@article{delorenzo_mathews_brandon_joglekar_baez_moore_ciccotto_roberts_roberts_powder_2023, title={Genetic basis of ecologically relevant body shape variation among four genera of cichlid fishes}, volume={5}, ISSN={["1365-294X"]}, DOI={10.1111/mec.16977}, abstractNote={Abstract}, journal={MOLECULAR ECOLOGY}, author={DeLorenzo, Leah and Mathews, Destiny and Brandon, A. Allyson and Joglekar, Mansi and Baez, Aldo Carmona and Moore, Emily C. and Ciccotto, Patrick J. and Roberts, Natalie B. and Roberts, Reade B. and Powder, Kara E.}, year={2023}, month={May} }
 @article{delorenzo_debrock_baez_ciccotto_peterson_stull_roberts_roberts_powder_2022, title={Morphometric and Genetic Description of Trophic Adaptations in Cichlid Fishes}, volume={11}, ISSN={["2079-7737"]}, url={https://www.mdpi.com/2079-7737/11/8/1165}, DOI={10.3390/biology11081165}, abstractNote={Since Darwin, biologists have sought to understand the evolution and origins of phenotypic adaptations. The skull is particularly diverse due to intense natural selection on feeding biomechanics. We investigated the genetic and molecular origins of trophic adaptation using Lake Malawi cichlids, which have undergone an exemplary evolutionary radiation. We analyzed morphological differences in the lateral and ventral head shape among an insectivore that eats by suction feeding, an obligate biting herbivore, and their F2 hybrids. We identified variation in a series of morphological traits—including mandible width, mandible length, and buccal length—that directly affect feeding kinematics and function. Using quantitative trait loci (QTL) mapping, we found that many genes of small effects influence these craniofacial adaptations. Intervals for some traits were enriched in genes related to potassium transport and sensory systems, the latter suggesting co-evolution of feeding structures and sensory adaptations for foraging. Despite these indications of co-evolution of structures, morphological traits did not show covariation. Furthermore, phenotypes largely mapped to distinct genetic intervals, suggesting that a common genetic basis does not generate coordinated changes in shape. Together, these suggest that craniofacial traits are mostly inherited as separate modules, which confers a high potential for the evolution of morphological diversity. Though these traits are not restricted by genetic pleiotropy, functional demands of feeding and sensory structures likely introduce constraints on variation. In all, we provide insights into the quantitative genetic basis of trophic adaptation, identify mechanisms that influence the direction of morphological evolution, and provide molecular inroads to craniofacial variation.}, number={8}, journal={BIOLOGY-BASEL}, author={DeLorenzo, Leah and DeBrock, Victoria and Baez, Aldo Carmona and Ciccotto, Patrick J. and Peterson, Erin N. and Stull, Clare and Roberts, Natalie B. and Roberts, Reade B. and Powder, Kara E.}, year={2022}, month={Aug} }
 @article{moore_ciccotto_peterson_lamm_albertson_roberts_2022, title={Polygenic sex determination produces modular sex polymorphism in an African cichlid fish}, volume={119}, ISSN={["1091-6490"]}, DOI={10.1073/pnas.2118574119}, abstractNote={Significance}, number={14}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Moore, Emily C. and Ciccotto, Patrick J. and Peterson, Erin N. and Lamm, Melissa S. and Albertson, R. Craig and Roberts, Reade B.}, year={2022}, month={Apr} }
 @article{watson_carmona baez_jima_reif_ding_roberts_kullman_2022, title={TCDD alters essential transcriptional regulators of osteogenic differentiation in multipotent mesenchymal stem cells}, volume={11}, ISSN={["1096-0929"]}, url={https://doi.org/10.1093/toxsci/kfac120}, DOI={10.1093/toxsci/kfac120}, abstractNote={Abstract}, journal={TOXICOLOGICAL SCIENCES}, author={Watson, AtLee T. D. and Carmona Baez, Aldo and Jima, Dereje and Reif, David and Ding, Jun and Roberts, Reade and Kullman, Seth W.}, year={2022}, month={Nov} }
 @article{conte_clark_roberts_xu_tao_zhou_wang_kocher_2021, title={Origin of a Giant Sex Chromosome}, volume={38}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/msaa319}, abstractNote={Abstract}, number={4}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Conte, Matthew A. and Clark, Frances E. and Roberts, Reade B. and Xu, Luohao and Tao, Wenjing and Zhou, Qi and Wang, Deshou and Kocher, Thomas D.}, year={2021}, month={Apr}, pages={1554–1569} }
 @article{johnson_moore_wong_godwin_streelman_roberts_2020, title={Exploratory behaviour is associated with microhabitat and evolutionary radiation in Lake Malawi cichlids}, volume={160}, ISSN={["1095-8282"]}, DOI={10.1016/j.anbehav.2019.11.006}, abstractNote={Encountering and adaptively responding to unfamiliar or novel stimuli is a fundamental challenge facing animals and is linked to fitness. Behavioural responses to novel stimuli can differ strongly between closely related species; however, the ecological and evolutionary factors underlying these differences are not well understood, in part because most comparative investigations have focused on only two species. In this study, we investigate behavioural responses to novel environments, or exploratory behaviours, sampling from a total of 20 species in a previously untested vertebrate system, Lake Malawi cichlid fishes, which comprises hundreds of phenotypically diverse species that have diverged in the past one million years. We show generally conserved behavioural response patterns to different types of environmental stimuli in Lake Malawi cichlids, spanning multiple assays and paralleling other teleost and rodent lineages. Next, we demonstrate that more specific dimensions of exploratory behaviour vary strongly among Lake Malawi cichlids, and that a large proportion of this variation is explained by species differences. We further show that species differences in open field behaviours are explained by microhabitat and by a major evolutionary split between the mbuna and benthic/utaka radiations in Lake Malawi. Lastly, we track some individuals across a subset of behavioural assays and show that patterns of behavioural covariation across contexts are characteristic of modular complex traits. Taken together, our results tie ecology and evolution to natural behavioural variation, and highlight Lake Malawi cichlids as a powerful system for understanding the biological basis of exploratory behaviours.}, journal={ANIMAL BEHAVIOUR}, author={Johnson, Zachary V and Moore, Emily C. and Wong, Ryan Y. and Godwin, John R. and Streelman, Jeffrey T. and Roberts, Reade B.}, year={2020}, month={Feb}, pages={121–134} }
 @article{conte_joshi_moore_nandamuri_gammerdinger_roberts_carleton_lien_kocher_2019, title={Chromosome-scale assemblies reveal the structural evolution of African cichlid genomes}, volume={8}, ISSN={["2047-217X"]}, DOI={10.1093/gigascience/giz030}, abstractNote={African cichlid fishes are well known for their rapid radiations and are a model system for studying evolutionary processes. Here we compare multiple, high-quality, chromosome-scale genome assemblies to elucidate the genetic mechanisms underlying cichlid diversification and study how genome structure evolves in rapidly radiating lineages. We re-anchored our recent assembly of the Nile tilapia (Oreochromis niloticus) genome using a new high-density genetic map. We also developed a new de novo genome assembly of the Lake Malawi cichlid, Metriaclima zebra, using high-coverage Pacific Biosciences sequencing, and anchored contigs to linkage groups (LGs) using 4 different genetic maps. These new anchored assemblies allow the first chromosome-scale comparisons of African cichlid genomes. Large intra-chromosomal structural differences (∼2–28 megabase pairs) among species are common, while inter-chromosomal differences are rare (<10 megabase pairs total). Placement of the centromeres within the chromosome-scale assemblies identifies large structural differences that explain many of the karyotype differences among species. Structural differences are also associated with unique patterns of recombination on sex chromosomes. Structural differences on LG9, LG11, and LG20 are associated with reduced recombination, indicative of inversions between the rock- and sand-dwelling clades of Lake Malawi cichlids. M. zebra has a larger number of recent transposable element insertions compared with O. niloticus, suggesting that several transposable element families have a higher rate of insertion in the haplochromine cichlid lineage. This study identifies novel structural variation among East African cichlid genomes and provides a new set of genomic resources to support research on the mechanisms driving cichlid adaptation and speciation.}, number={4}, journal={GIGASCIENCE}, author={Conte, Matthew A. and Joshi, Rajesh and Moore, Emily C. and Nandamuri, Sri Pratima and Gammerdinger, William J. and Roberts, Reade B. and Carleton, Karen L. and Lien, Sigbjorn and Kocher, Thomas D.}, year={2019}, month={Apr} }
 @article{reiskind_reed_elias_giacomini_mcnear_nieuwsma_parker_roberts_rossi_stephenson_et al._2019, title={The genomics of invasion: characterization of red lionfish (Pterois volitans) populations from the native and introduced ranges}, volume={21}, ISSN={["1573-1464"]}, url={http://dx.doi.org/10.1007/s10530-019-01992-0}, DOI={10.1007/s10530-019-01992-0}, number={7}, journal={BIOLOGICAL INVASIONS}, author={Reiskind, M. O. Burford and Reed, E. M. X. and Elias, A. and Giacomini, J. J. and McNear, A. F. and Nieuwsma, J. and Parker, G. A. and Roberts, R. B. and Rossi, R. E. and Stephenson, C. N. and et al.}, year={2019}, month={Jul}, pages={2471–2483} }
 @article{reiskind_reed_elias_giacomini_mcnear_nieuwsma_parker_roberts_rossi_stephenson_et al._2019, title={The genomics of invasion: characterization of red lionfish (Pterois volitans) populations from the native and introduced ranges (vol 21, pg 2471, 2019)}, volume={21}, ISSN={["1573-1464"]}, DOI={10.1007/s10530-019-01999-7}, abstractNote={In the original publication of this article, Figs. 2 and 3 were published incorrectly.}, number={7}, journal={BIOLOGICAL INVASIONS}, author={Reiskind, M. O. Burford and Reed, E. M. X. and Elias, A. and Giacomini, J. J. and McNear, A. F. and Nieuwsma, J. and Parker, G. A. and Roberts, R. B. and Rossi, R. E. and Stephenson, C. N. and et al.}, year={2019}, month={Jul}, pages={2485–2487} }
 @article{faber-hammond_coyle_bacheller_roberts_mellies_roberts_renn_2019, title={The intestinal environment as an evolutionary adaptation to mouthbrooding in the Astatotilapia burtoni cichlid}, volume={95}, ISSN={["1574-6941"]}, DOI={10.1093/femsec/fiz016}, abstractNote={ABSTRACT}, number={3}, journal={FEMS MICROBIOLOGY ECOLOGY}, author={Faber-Hammond, Josh J. and Coyle, Kaitlin P. and Bacheller, Shannon K. and Roberts, Cameron G. and Mellies, Jay L. and Roberts, Reade B. and Renn, Suzy C. P.}, year={2019}, month={Mar} }
 @article{stuckert_moore_coyle_davison_macmanes_roberts_summers_2019, title={Variation in pigmentation gene expression is associated with distinct aposematic color morphs in the poison frog Dendrobates auratus}, volume={19}, ISSN={["1471-2148"]}, DOI={10.1186/s12862-019-1410-7}, abstractNote={Color and pattern phenotypes have clear implications for survival and reproduction in many species. However, the mechanisms that produce this coloration are still poorly characterized, especially at the genomic level. Here we have taken a transcriptomics-based approach to elucidate the underlying genetic mechanisms affecting color and pattern in a highly polytypic poison frog. We sequenced RNA from the skin from four different color morphs during the final stage of metamorphosis and assembled a de novo transcriptome. We then investigated differential gene expression, with an emphasis on examining candidate color genes from other taxa.Overall, we found differential expression of a suite of genes that control melanogenesis, melanocyte differentiation, and melanocyte proliferation (e.g., tyrp1, lef1, leo1, and mitf) as well as several differentially expressed genes involved in purine synthesis and iridophore development (e.g., arfgap1, arfgap2, airc, and gart).Our results provide evidence that several gene networks known to affect color and pattern in vertebrates play a role in color and pattern variation in this species of poison frog.}, journal={BMC EVOLUTIONARY BIOLOGY}, author={Stuckert, Adam M. M. and Moore, Emily and Coyle, Kaitlin P. and Davison, Ian and MacManes, Matthew D. and Roberts, Reade and Summers, Kyle}, year={2019}, month={Apr} }
 @inbook{godwin_roberts_2018, title={Environmental and Genetic Sex Determining Mechanisms in Fishes}, ISBN={9783319941370 9783319941394}, url={http://dx.doi.org/10.1007/978-3-319-94139-4_11}, DOI={10.1007/978-3-319-94139-4_11}, booktitle={Transitions Between Sexual Systems}, publisher={Springer International Publishing}, author={Godwin, John and Roberts, Reade}, year={2018}, pages={311–344} }
 @article{roberts_moore_kocher_2017, title={An allelic series at pax7a is associated with colour polymorphism diversity in Lake Malawi cichlid fish}, volume={26}, ISSN={["1365-294X"]}, DOI={10.1111/mec.13975}, abstractNote={Abstract}, number={10}, journal={MOLECULAR ECOLOGY}, author={Roberts, Reade B. and Moore, Emily C. and Kocher, Thomas D.}, year={2017}, month={May}, pages={2625–2639} }
 @article{peterson_cline_moore_roberts_roberts_2017, title={Genetic sex determination in Astatotilapia calliptera, a prototype species for the Lake Malawi cichlid radiation}, volume={104}, ISSN={["1432-1904"]}, DOI={10.1007/s00114-017-1462-8}, abstractNote={East African cichlids display extensive variation in sex determination systems. The species Astatotilapia calliptera is one of the few cichlids that reside both in Lake Malawi and in surrounding waterways. A. calliptera is of interest in evolutionary studies as a putative immediate outgroup species for the Lake Malawi species flock and possibly as a prototype ancestor-like species for the radiation. Here, we use linkage mapping to test association of sex in A. calliptera with loci that have been previously associated with genetic sex determination in East African cichlid species. We identify a male heterogametic XY system segregating at linkage group (LG) 7 in an A. calliptera line that originated from Lake Malawi, at a locus previously shown to act as an XY sex determination system in multiple species of Lake Malawi cichlids. Significant association of genetic markers and sex produce a broad genetic interval of approximately 26 megabases (Mb) using the Nile tilapia genome to orient markers; however, we note that the marker with the strongest association with sex is near a gene that acts as a master sex determiner in other fish species. We demonstrate that alleles of the marker are perfectly associated with sex in Metriaclima mbenjii, a species from the rock-dwelling clade of Lake Malawi. While we do not rule out the possibility of other sex determination loci in A. calliptera, this study provides a foundation for fine mapping of the cichlid sex determination gene on LG7 and evolutionary context regarding the origin and persistence of the LG7 XY across diverse, rapidly evolving lineages.}, number={5-6}, journal={SCIENCE OF NATURE}, author={Peterson, Erin N. and Cline, Maggie E. and Moore, Emily C. and Roberts, Natalie B. and Roberts, Reade B.}, year={2017}, month={Jun} }
 @article{burford reiskind_coyle_daniels_labadie_reiskind_roberts_roberts_schaff_vargo_2016, title={Development of a universal double-digest RAD sequencing approach for a group of nonmodel, ecologically and economically important insect and fish taxa}, volume={16}, ISSN={1755-098X}, url={http://dx.doi.org/10.1111/1755-0998.12527}, DOI={10.1111/1755-0998.12527}, abstractNote={Abstract}, number={6}, journal={Molecular Ecology Resources}, publisher={Wiley}, author={Burford Reiskind, M. O. and Coyle, K. and Daniels, H. V. and Labadie, P. and Reiskind, M. H. and Roberts, N. B. and Roberts, R. B. and Schaff, J. and Vargo, E. L.}, year={2016}, month={May}, pages={1303–1314} }
 @article{moore_roberts_2016, title={Genital morphology and allometry differ by species and sex in Malawi cichlid fishes}, volume={791}, ISSN={0018-8158 1573-5117}, url={http://dx.doi.org/10.1007/s10750-016-2912-6}, DOI={10.1007/s10750-016-2912-6}, abstractNote={The African cichlid fishes show great diversity in mating displays and reproductive strategies, yet species differences in genital morphology have been little studied. Observational notes have described broad sex differences in external genital shape between males and females, but these differences have not been quantified. We examined three aspects of genital morphology (relative anogenital distance, relative vent length, and relative external genital area) in two riverine and eleven Lake Malawi African cichlid species from eight genera. We find the most sexually distinct morphology in the Lake Malawi rock cichlids and the least sexual dimorphism in the riverine outgroup; additionally, diversity in metrics within genus indicates that these traits are recently evolving. Sexual dimorphism in morphology is present in most species, and, in the Lake Malawi species, multivariate discriminant analysis allows for accurate assignment of gonadal sex based on genital morphology and body size. This will serve as a useful method for sexing fish in a nonlethal fashion and provides a starting point for further examination of the evolution of genital morphology in this diverse group of fishes.}, number={1}, journal={Hydrobiologia}, publisher={Springer Nature}, author={Moore, Emily C. and Roberts, Reade B.}, year={2016}, month={Jul}, pages={127–143} }
 @misc{abila_akoll_albertson_antunes_banda_bills_bulirani_manda_cohen_cunha-saraiva_et al._2016, title={Oil extraction imperils Africa's Great Lakes}, volume={354}, number={6312}, journal={Science}, author={Abila, R. and Akoll, P. and Albertson, C. and Antunes, D. and Banda, T. and Bills, R. and Bulirani, A. and Manda, A. C. and Cohen, A. S. and Cunha-Saraiva, F. and et al.}, year={2016}, pages={561–562} }
 @article{roberts_juntti_coyle_dumont_stanley_ryan_fernald_roberts_2016, title={Polygenic sex determination in the cichlid fish Astatotilapia burtoni}, volume={17}, ISSN={["1471-2164"]}, DOI={10.1186/s12864-016-3177-1}, abstractNote={The East African riverine cichlid species Astatotilapia burtoni serves as an important laboratory model for sexually dimorphic physiology and behavior, and also serves as an outgroup species for the explosive adaptive radiations of cichlid species in Lake Malawi and Lake Victoria. An astounding diversity of genetic sex determination systems have been revealed within the adaptive radiation of East African cichlids thus far, including polygenic sex determination systems involving the epistatic interaction of multiple, independently segregating sex determination alleles. However, sex determination has remained unmapped in A. burtoni. Here we present mapping results supporting the presence of multiple, novel sex determination alleles, and thus the presence of polygenic sex determination in A. burtoni.Using mapping in small families in conjunction with restriction-site associated DNA sequencing strategies, we identify associations with sex at loci on linkage group 13 and linkage group 5-14. Inheritance patterns support an XY sex determination system on linkage group 5-14 (a chromosome fusion relative to other cichlids studied), and an XYW system on linkage group 13, and these associations are replicated in multiple families. Additionally, combining our genetic data with comparative genomic analysis identifies another fusion that is unassociated with sex, with linkage group 8-24 and linkage group 16-21 fused in A. burtoni relative to other East African cichlid species.We identify genetic signals supporting the presence of three previously unidentified sex determination alleles at two loci in the species A. burtoni, strongly supporting the presence of polygenic sex determination system in the species. These results provide a foundation for future mapping of multiple sex determination genes and their interactions. A better understanding of sex determination in A. burtoni provides important context for their use in behavioral studies, as well as studies of the evolution of genetic sex determination and sexual conflicts in East African cichlids.}, journal={BMC GENOMICS}, author={Roberts, Natalie B. and Juntti, Scott A. and Coyle, Kaitlin P. and Dumont, Bethany L. and Stanley, M. Kaitlyn and Ryan, Allyson Q. and Fernald, Russell D. and Roberts, Reade B.}, year={2016}, month={Oct} }
 @article{albertson_powder_hu_coyle_roberts_parsons_2014, title={Genetic basis of continuous variation in the levels and modular inheritance of pigmentation in cichlid fishes}, volume={23}, ISSN={["1365-294X"]}, DOI={10.1111/mec.12900}, abstractNote={Abstract}, number={21}, journal={MOLECULAR ECOLOGY}, author={Albertson, R. Craig and Powder, Kara E. and Hu, Yinan and Coyle, Kaitlin P. and Roberts, Reade B. and Parsons, Kevin J.}, year={2014}, month={Nov}, pages={5135–5150} }
 @article{gammerdinger_conte_acquah_roberts_kocher_2014, title={Structure and decay of a proto-Y region in Tilapia, Oreochromis niloticus}, volume={15}, ISSN={1471-2164}, url={http://dx.doi.org/10.1186/1471-2164-15-975}, DOI={10.1186/1471-2164-15-975}, abstractNote={Sex-determination genes drive the evolution of adjacent chromosomal regions. Sexually antagonistic selection favors the accumulation of inversions that reduce recombination in regions adjacent to the sex-determination gene. Once established, the clonal inheritance of sex-linked inversions leads to the accumulation of deleterious alleles, repetitive elements and a gradual decay of sex-linked genes. This in turn creates selective pressures for the evolution of mechanisms that compensate for the unequal dosage of gene expression. Here we use whole genome sequencing to characterize the structure of a young sex chromosome and quantify sex-specific gene expression in the developing gonad. We found an 8.8 Mb block of strong differentiation between males and females that corresponds to the location of a previously mapped sex-determiner on linkage group 1 of Oreochromis niloticus. Putatively disruptive mutations are found in many of the genes within this region. We also found a significant female-bias in the expression of genes within the block of differentiation compared to those outside the block of differentiation. Eight candidate sex-determination genes were identified within this region. This study demonstrates a block of differentiation on linkage group 1, suggestive of an 8.8 Mb inversion encompassing the sex-determining locus. The enrichment of female-biased gene expression inside the proposed inversion suggests incomplete dosage compensation. This study helps establish a model for studying the early-to-intermediate stages of sex chromosome evolution.}, number={1}, journal={BMC Genomics}, publisher={Springer Nature}, author={Gammerdinger, William J and Conte, Matthew A and Acquah, Enoch A and Roberts, Reade B and Kocher, Thomas D}, year={2014}, pages={975} }
 @article{moore_roberts_2013, title={Polygenic sex determination}, volume={23}, ISSN={["0960-9822"]}, DOI={10.1016/j.cub.2013.04.004}, abstractNote={What is sex determination? Sex determination is the mechanism by which sexual organisms direct gonad development towards distinct but reproductively compatible outcomes. Molecular signaling cascades in the developing gonad provide instructions to the tissue to develop as male or female (or in some cases hermaphrodite), and these signals can be initiated in different ways. Sex can be determined by environmental cues (such as temperature), or genetically. Genetic sex determination occurs when an inherited difference in genes or chromosomes initiates the sex determination signal, acting as a ‘master switch’ for male or female development. Perhaps the most widely known genetic sex determination system is the male heterogametic XX/XY system found in most mammals, where the Sry gene on the Y chromosome determines male sex. Thus, XY individuals develop as males, and XX individuals develop as females. Many other organisms, including birds, have a ZZ/ZW chromosomal system, where heterogametic ZW individuals develop as female, and homogametic ZZ individuals develop as male (Figure 1). How is polygenic sex determination different? In the XY and ZW systems described above, a single genetic locus, often on a morphologically distinct chromosome, acts as the master switch for sex determination. In polygenic sex determination (PSD), multiple, independently segregating sex ‘switch’ loci or alleles determine sex within a species. Polygenic systems can arise through modifications of existing sex chromosomes that create a third functional sex chromosome at the same locus, or through modifications of autosomal loci elsewhere in the genome that create new inputs for regulation of gonad development. The term ‘polygenic sex determination’ appears to have been coined by Kosswig around 1964, shortly after PSD was described in platyfish (Xiphophorus spp.). In the case of platyfish, some populations have both a Y male determination allele and a W female determination allele segregating at the same chromosome pair. Despite the discovery and description of PSD nearly fifty years ago, the phenomenon remains relatively unknown, and only recently have we begun realizing the potential extent of PSD systems across taxa. What species have PSD? Polygenic sex determination is known to occur naturally in various species of insects, mammals, fish, and plants. Some housefly (Musca domestica) populations have male and female sex determination loci on autosomes in addition to a male sex determiner on a morphologically distinct Y chromosome. Among vertebrates, birds and mammals generally have evolutionarily conserved monogenic sex determination systems; however, African pygmy mice (Mus minutoides), some species of South American field mice (Akodon spp.) and two species of lemmings (Myopus schisticolor and Dicrostonyx torquatus) have independently evolved an additional, independently assorting female sex determination locus. Fish have been the most well studied vertebrate lineage with regard to variety of sex determination mechanisms, and it is within this group that PSD was initially discovered. Additional examples of PSD have recently been found in fish, including in African cichlid fish (Metriaclima spp.) and the developmental model zebrafish (Danio rerio). Outside of the animal kingdom, some gynodioecious plants (such as Thymus vulgaris and Plantago coronopus) appear to determine hermaphroditic versus female sex through interactions of multiple cytoplasmic and nuclear loci. Do all species with multiple sex chromosomes have PSD? Not necessarily. For example, the platypus (Orinthorhynchus anatinus) has five sex chromosome pairs — males have five X and five Y chromosomes. However, these chromosomes form chains and segregate together during meiosis, so that they effectively behave as a single X and a single Y chromosome when distributed to gametes, rather than five independently segregating pairs of chromosomes. Similar scenarios occur in sticklebacks and other fishes, where multiple sex chromosomes are present, but pair in such a way as to consistently segregate as if they were a single chromosome pair. Since there do not appear to be multiple genetic sex switch loci, and the sex chromosomes are not segregating independently, these cases do not meet the requirements of the PSD definition above. In PSD, which sex determination locus ‘wins’ to determine sex? The locus that wins and ultimately determines the fate of the gonad depends on the system being examined (Figure 1). In platyfish, pygmy mice, and lemmings, the ancestral state was an XY system. In these cases, one of the X chromosomes gained a female sex-determination allele that is dominant to the Y, directing ovary development in WY (also referred to as X∗Y) individuals. Some species of cichlid fish from Lake Malawi have an XY locus and a WZ locus on distinct chromosome pairs, and when these occur in the same individual, the W female determiner wins, and the individual develops as female. The end result of PSD is not always skewed towards females; in some housefly populations, a sex determination locus on an autosome causes XX flies to develop as male. In other cases, including zebrafish and cichlids, sex determination likely results from a combination of additive and epistatic effects at many loci. Thus, an allele that wins in one combination of sex determination loci genotypes may lose in another. Indeed, in some gynodioecious plants, the outcome of a genetic contest between ‘anti-male’ mitochondrial loci and nuclear ‘pro-male’ restorer loci ultimately determines female versus hermaphrodite development. Truly, there is striking diversity in the different ways PSD has independently evolved across these taxa. Why haven’t I heard of PSD before? Simply put, historical and technical bias. Genetic sex determination was first identified in insects, where it was found in the form simplest to detect and easiest to understand: a single, highly differentiated sex chromosome was found in one sex but not the other. This precedent was confirmed in mammals, birds, and important model systems like Drosophila melanogaster. Later, additional types of chromosome-level sex determination were identified, including XO systems (found in the nematode Caenorhabditis elegans) and haploid–diploid systems (found in Hymenopteran insects, including ants and bees). The ease of studying chromosomal sex, where sex chromosomes could be readily identified under a microscope, surely biased the study of sex determination against autosomal sex determination loci systems for the greater part of the last century. Since this historical bias had a large conceptual impact on the study of biology from evolutionary theory to developmental research, PSD systems may have remained largely undiscovered, or, when they were identified, dismissed as odd exceptions to the rule. Early studies of sex ratios in some species suggested PSD, but until relatively recently, the technology was not available to readily identify multiple, interacting sex determination loci in many species. With the advent of less expensive genome sequencing, and more sophisticated strategies for genetic mapping, we expect that instances of PSD will become easier to find, and the catalog of examples will grow. In fact, some species traditionally thought to have a monogenic sex determination system may demonstrably have PSD upon further study, including those species for which sex determination has not been examined or has only been examined in a small number of families or populations. For example, when mapping sex determination in some African cichlids, PSD could be missed by chance sampling of families whose parents carry only one sex determiner (e.g., a cross between a ZZ/XY male and a ZZ/XX female would allow mapping of the XY locus, but not the ZW locus). Ultimately, discovery of PSD systems requires truly representative mapping strategies as well as openness to the possibility that multiple sex determination loci may be segregating in a population. Why does PSD exist? One hypothesis to explain the evolution of PSD is that a novel sex determination locus will be maintained if it provides a benefit to individuals carrying it. For example, in both houseflies and South American field mice, individuals with the more recently evolved sex determination alleles have higher reproductive fitness. It is unclear whether the gene that acts as the overriding primary sex switch has pleiotropic effects modulating fitness, or if the novel sex determination locus is linked to another gene that provides enhanced fitness. Novel sex determination loci may also arise and be maintained if they resolve a sexual conflict involving an allele that provides an adaptive benefit to one sex to the detriment of the other. Such a scenario appears in African cichlid fish, where a pigmentation allele provides camouflage to females, but disrupts sexually selected male nuptial color and thus reduces male mating success. The pigmentation allele is tightly linked to a recently evolved female sex determination locus, ensuring that the color trait will only be expressed in females, the benefiting sex. Similar sexual conflicts could be evolutionarily intertwined with each sex determination locus in PSD systems. Is PSD evolutionarily stable? The answer is not entirely clear. One argument against stable PSD is that one sex determination allele would provide a reproductive fitness benefit over another, and selection would fix it as the sole sex determiner. Another concern is that PSD could produce highly skewed sex ratios, depending on the number of loci and how they interact. However, depending on how different sex switches are integrated during sexual development, and the frequencies of sex determination alleles in populations, these arguments may not be valid in all circumstances. In a simple sense, PSD systems may be inherently unstable if they can easily revert to single factor systems by loss of sex determination loci via drift or selection. In some species with PSD (such as houseflies and cichlids), sex determination occurs normally if only a single genetic factor is present, and different populations appear to have monogenic versus polygenic sex determination. Thus, it appears that only a single genetic switch is required for proper sexual reproduction in these species, even though multiple sex determination loci can be present. However, we suggest that the widespread presence of PSD across taxa suggests that it represents an evolutionarily stable strategy in some scenarios. The alternative would require that the examples cataloged thus far all represent temporary destabilization of a fundamental fitness trait in species, or evolutionary transitions between sex determination systems. One hypothesis for the stability of PSD is that it could readily produce multiple phenotypic or reproductive classes within a sex, or more than two sex types. If these class or type differences result in alternative fitness benefits, selection may maintain them in the population, contributing to PSD being an evolutionarily stable scenario. How many sexes are there? The traditional view of primary, gonadal sex is of a binary trait — each individual is either male or female. With multiple interacting loci determining primary sex, there are as many genetic sexes for a given group as there are possible combinations of sex determination loci. In known cases of PSD in animals, primary sex remains binary, but evidence suggests that genotypically different individuals of the same primary sex can have differential reproductive success, as mentioned above. Thus, even though primary sex may be binary in these cases, PSD may produce different classes within a single sex, or individuals of the same primary sex with strikingly different secondary sexual characteristics. In some plants, PSD systems may produce what could be considered more than two sexes. For example, in the domesticated cantaloupe, Cucumis melo, multiple loci interact to produce four sexes, with andromonoecious, monoecious, gynoecious, and hermaphrodite individuals in some cultivars (though it is not clear if such a system occurs naturally). In light of the variability in the genetic controls of sex determination and development, it may be beneficial to re-evaluate our view of sex as a binary trait. Why study PSD? Organisms with PSD provide us with models of multiple genetic switches that interact in different combinations to produce a fundamental fitness phenotype and resounding effects throughout an organism. These models can be used to study the evolution of gene networks and epistasis, and allow us to ask questions about the developmental regulation of genes that are traditionally thought of as members of core sex signaling networks. Species with PSD also provide snapshots of possible transitions from one mode of sex determination to another, providing insight into the evolution of sex determination. Identification of additional sex determination genes and interactions should also provide insight into sexual development and disease. Ultimately, studying intrasex differences in PSD models may provide insight into the continuum of sex differences in humans, and challenge long held notions of the evolution and development of sex and sexual dimorphism.}, number={12}, journal={CURRENT BIOLOGY}, author={Moore, Emily C. and Roberts, Reade B.}, year={2013}, month={Jun}, pages={R510–R512} }
 @article{o'quin_drilea_roberts_kocher_2012, title={A Small Number of Genes Underlie Male Pigmentation Traits in Lake Malawi Cichlid Fishes}, volume={318}, ISSN={1552-5007}, url={http://dx.doi.org/10.1002/jez.b.22006}, DOI={10.1002/jez.b.22006}, abstractNote={Pigmentation patterns are one of the most recognizable forms of phenotypic diversity and an important component of organismal fitness. While much progress has been made in understanding the genes controlling pigmentation in model systems, many questions remain about the genetic basis of pigment traits observed in nature. Lake Malawi cichlid fishes are known for their diversity of male pigmentation patterns, which have been shaped by sexual selection. To begin the process of identifying the genes underlying this diversity, we quantified the number of pigment cells on the body and fins of two species of the genus Metriaclima and their hybrids. We then used the Castle-Wright equation to estimate that differences in individual pigmentation traits between these species are controlled by one to four genes each. Different pigmentation traits are highly correlated in the F(2) , suggesting shared developmental pathways and genetic pleiotropy. Melanophore and xanthophore traits fall on opposite ends of the first principal component axis of the F(2) phenotypes, suggesting a tradeoff during the development of these two pigment cell types.}, number={3}, journal={Journal of Experimental Zoology Part B: Molecular and Developmental Evolution}, publisher={Wiley}, author={O'Quin, Claire T. and Drilea, Alexi C. and Roberts, Reade B. and Kocher, Thomas D.}, year={2012}, month={Apr}, pages={199–208} }
 @article{loh_bezault_muenzel_roberts_swofford_barluenga_kidd_howe_di palma_lindblad-toh_et al._2012, title={Origins of Shared Genetic Variation in African Cichlids}, volume={30}, ISSN={1537-1719 0737-4038}, url={http://dx.doi.org/10.1093/molbev/mss326}, DOI={10.1093/molbev/mss326}, abstractNote={Cichlid fishes have evolved tremendous morphological and behavioral diversity in the waters of East Africa. Within each of the Great Lakes Tanganyika, Malawi, and Victoria, the phenomena of hybridization and retention of ancestral polymorphism explain allele sharing across species. Here, we explore the sharing of single nucleotide polymorphisms (SNPs) between the major East African cichlid assemblages. A set of approximately 200 genic and nongenic SNPs was ascertained in five Lake Malawi species and genotyped in a diverse collection of ∼160 species from across Africa. We observed segregating polymorphism outside of the Malawi lineage for more than 50% of these loci; this holds similarly for genic versus nongenic SNPs, as well as for SNPs at putative CpG versus non-CpG sites. Bayesian and principal component analyses of genetic structure in the data demonstrate that the Lake Malawi endemic flock is not monophyletic and that river species have likely contributed significantly to Malawi genomes. Coalescent simulations support the hypothesis that river cichlids have transported polymorphism between lake assemblages. We observed strong genetic differentiation between Malawi lineages for approximately 8% of loci, with contributions from both genic and nongenic SNPs. Notably, more than half of these outlier loci between Malawi groups are polymorphic outside of the lake. Cichlid fishes have evolved diversity in Lake Malawi as new mutations combined with standing genetic variation shared across East Africa.}, number={4}, journal={Molecular Biology and Evolution}, publisher={Oxford University Press (OUP)}, author={Loh, Yong-Hwee E. and Bezault, Etienne and Muenzel, Frauke M. and Roberts, Reade B. and Swofford, Ross and Barluenga, Marta and Kidd, Celeste E. and Howe, Aimee E. and Di Palma, Federica and Lindblad-Toh, Kerstin and et al.}, year={2012}, month={Dec}, pages={906–917} }
 @article{roberts_hu_albertson_kocher_2011, title={Craniofacial divergence and ongoing adaptation via the hedgehog pathway}, volume={108}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.1018456108}, DOI={10.1073/pnas.1018456108}, abstractNote={
            Adaptive variation in craniofacial structure contributes to resource specialization and speciation, but the genetic loci that underlie craniofacial adaptation remain unknown. Here we show that alleles of the hedgehog pathway receptor
            Patched1
            (
            Ptch1
            ) gene are responsible for adaptive variation in the shape of the lower jaw both within and among genera of Lake Malawi cichlid fish. The evolutionarily derived allele of
            Ptch1
            reduces the length of the retroarticular (RA) process of the lower jaw, a change predicted to increase speed of jaw rotation for improved suction-feeding. The alternate allele is associated with a longer RA and a more robustly mineralized jaw, typical of species that use a biting mode of feeding. Genera with the most divergent feeding morphologies are nearly fixed for different
            Ptch1
            alleles, whereas species with intermediate morphologies still segregate variation at
            Ptch1
            . Thus, the same alleles that help to define macroevolutionary divergence among genera also contribute to microevolutionary fine-tuning of adaptive traits within some species. Variability of craniofacial morphology mediated by
            Ptch1
            polymorphism has likely contributed to niche partitioning and ecological speciation of these fishes.
          }, number={32}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Roberts, Reade B. and Hu, Yinan and Albertson, R. Craig and Kocher, Thomas D.}, year={2011}, month={Jul}, pages={13194–13199} }
 @article{ser_roberts_kocher_2010, title={MULTIPLE INTERACTING LOCI CONTROL SEX DETERMINATION IN LAKE MALAWI CICHLID FISH}, volume={64}, ISSN={0014-3820 1558-5646}, url={http://dx.doi.org/10.1111/j.1558-5646.2009.00871.x}, DOI={10.1111/j.1558-5646.2009.00871.x}, abstractNote={Several models have been proposed to suggest how the evolution of sex‐determining mechanisms might contribute to speciation. Here, we describe the inheritance of sex in 19 fish species from the rapidly evolving flock of cichlids in Lake Malawi, Africa. We found that many of these species have a male heterogametic (XY) system on linkage group 7. Some species also segregate for a female heterogametic (ZW) system on linkage group 5 that is coincident with a dominant orange‐blotch (OB) color pattern in females. The ZW system is epistatically dominant to the XY system when both are segregating within a family. Several lines of evidence suggest that additional sex‐determining loci are segregating in some species. These results are consistent with the idea that genetic conflicts play an important role in the evolution of these species flocks and suggest that evolution of sex‐determining mechanisms has contributed to the radiation of cichlid fish in East Africa.}, number={2}, journal={Evolution}, publisher={Wiley}, author={Ser, Jennifer R. and Roberts, Reade B. and Kocher, Thomas D.}, year={2010}, month={Feb}, pages={486–501} }
 @article{barrick_roberts_rojas_rajamannan_suitt_o'brien_smyth_threadgill_2009, title={Reduced EGFR causes abnormal valvular differentiation leading to calcific aortic stenosis and left ventricular hypertrophy in C57BL/6J but not 129S1/SvImJ mice}, volume={297}, ISSN={0363-6135 1522-1539}, url={http://dx.doi.org/10.1152/ajpheart.00866.2008}, DOI={10.1152/ajpheart.00866.2008}, abstractNote={ Epidermal growth factor receptor (EGFR) signaling contributes to aortic valve development in mice. Because developmental phenotypes in Egfr-null mice are dependent on genetic background, the hypomorphic Egfr wa2 allele was made congenic on C57BL/6J (B6) and 129S1/SvImJ (129) backgrounds and used to identify the underlying cellular cause of EGFR-related aortic valve abnormalities. Egfr wa2/wa2 mice on both genetic backgrounds develop aortic valve hyperplasia. Many B6- Egfr wa2/wa2 mice die before weaning, and those surviving to 3 mo of age or older develop severe left ventricular hypertrophy and heart failure. The cardiac phenotype was accompanied by significantly thicker aortic cusps and larger transvalvular gradients in B6- Egfr wa2/wa2 mice compared with heterozygous controls and age-matched Egfr wa2 homozygous mice on either 129 or B6129F1 backgrounds. Histological analysis revealed cellular changes in B6- Egfr wa2/wa2 aortic valves underlying elevated pressure gradients and progression to heart failure, including increased cellular proliferation, ectopic cartilage formation, extensive calcification, and inflammatory infiltrate, mimicking changes seen in human calcific aortic stenosis. Despite having congenitally enlarged valves, 129 and B6129F1- Egfr wa2/wa2 mice have normal lifespans, absence of left ventricular hypertrophy, and normal systolic function. These results show the requirement of EGFR activity for normal valvulogenesis and demonstrate that dominantly acting genetic modifiers curtail pathological changes in congenitally deformed valves. These studies provide a novel model of aortic sclerosis and stenosis and suggest that long-term inhibition of EGFR signaling for cancer therapy may have unexpected consequences on aortic valves in susceptible individuals. }, number={1}, journal={American Journal of Physiology-Heart and Circulatory Physiology}, publisher={American Physiological Society}, author={Barrick, Cordelia J. and Roberts, Reade B. and Rojas, Mauricio and Rajamannan, Nalini M. and Suitt, Carolyn B. and O'Brien, Kevin D. and Smyth, Susan S. and Threadgill, David W.}, year={2009}, month={Jul}, pages={H65–H75} }
 @article{roberts_ser_kocher_2009, title={Sexual Conflict Resolved by Invasion of a Novel Sex Determiner in Lake Malawi Cichlid Fishes}, volume={326}, ISSN={0036-8075 1095-9203}, url={http://dx.doi.org/10.1126/science.1174705}, DOI={10.1126/science.1174705}, abstractNote={Sexual Blotch}, number={5955}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Roberts, R. B. and Ser, J. R. and Kocher, T. D.}, year={2009}, month={Oct}, pages={998–1001} }
 @article{kaiser_park_franklin_halberg_yu_jessen_freudenberg_chen_haigis_jegga_et al._2007, title={Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer}, volume={8}, ISSN={1465-6906}, url={http://dx.doi.org/10.1186/gb-2007-8-7-r131}, DOI={10.1186/gb-2007-8-7-r131}, abstractNote={The expression of carcino-embryonic antigen by colorectal cancer is an example of oncogenic activation of embryonic gene expression. Hypothesizing that oncogenesis-recapitulating-ontogenesis may represent a broad programmatic commitment, we compared gene expression patterns of human colorectal cancers (CRCs) and mouse colon tumor models to those of mouse colon development embryonic days 13.5-18.5.We report here that 39 colon tumors from four independent mouse models and 100 human CRCs encompassing all clinical stages shared a striking recapitulation of embryonic colon gene expression. Compared to normal adult colon, all mouse and human tumors over-expressed a large cluster of genes highly enriched for functional association to the control of cell cycle progression, proliferation, and migration, including those encoding MYC, AKT2, PLK1 and SPARC. Mouse tumors positive for nuclear beta-catenin shifted the shared embryonic pattern to that of early development. Human and mouse tumors differed from normal embryonic colon by their loss of expression modules enriched for tumor suppressors (EDNRB, HSPE, KIT and LSP1). Human CRC adenocarcinomas lost an additional suppressor module (IGFBP4, MAP4K1, PDGFRA, STAB1 and WNT4). Many human tumor samples also gained expression of a coordinately regulated module associated with advanced malignancy (ABCC1, FOXO3A, LIF, PIK3R1, PRNP, TNC, TIMP3 and VEGF).Cross-species, developmental, and multi-model gene expression patterning comparisons provide an integrated and versatile framework for definition of transcriptional programs associated with oncogenesis. This approach also provides a general method for identifying pattern-specific biomarkers and therapeutic targets. This delineation and categorization of developmental and non-developmental activator and suppressor gene modules can thus facilitate the formulation of sophisticated hypotheses to evaluate potential synergistic effects of targeting within- and between-modules for next-generation combinatorial therapeutics and improved mouse models.}, number={7}, journal={Genome Biology}, publisher={Springer Nature}, author={Kaiser, Sergio and Park, Young-Kyu and Franklin, Jeffrey L and Halberg, Richard B and Yu, Ming and Jessen, Walter J and Freudenberg, Johannes and Chen, Xiaodi and Haigis, Kevin and Jegga, Anil G and et al.}, year={2007}, pages={R131} }
 @article{roberts_thompson_lee_mankinen_sancar_threadgill_2006, title={Wildtype epidermal growth factor receptor (Egfr) is not required for daily locomotor or masking behavior in mice}, volume={4}, ISSN={1740-3391}, url={http://dx.doi.org/10.1186/1740-3391-4-15}, DOI={10.1186/1740-3391-4-15}, abstractNote={Recent studies have implicated the epidermal growth factor receptor (EGFR) within the subparaventricular zone as being a major mediator of locomotor and masking behaviors in mice. The results were based on small cohorts of mice homozygous for the hypomorphic Egfrwa2 allele on a mixed, genetically uncontrolled background, and on intraventricular infusion of exogenous EGFR ligands. Subsequenlty, a larger study using the same genetically mixed background failed to replicate the original findings. Since both previous approaches were susceptible to experimental artifacts related to an uncontrolled genetic background, we analyzed the locomotor behaviors in Egfrwa2 mutant mice on genetically defined, congenic backgrounds.Mice carrying the Egfrwa2 hypomorphic allele were bred to congenicity by backcrossing greater than ten generations onto C57BL/6J and 129S1/SvImJ genetic backgrounds. Homozygous Egfrwa2 mutant and wildtype littermates were evaluated for defects in locomotor and masking behaviors.Mice homozygous for Egfrwa2 showed normal daily locomotor activity and masking indistinguishable from wildtype littermates at two light intensities (200-300 lux and 400-500 lux).Our results demonstrate that reduced EGFR activity alone is insufficient to perturb locomotor and masking behaviors in mice. Our results also suggest that other uncontrolled genetic or environmental parameters confounded previous experiments linking EGFR activity to daily locomotor activity and provide a cautionary tale for genetically uncontrolled studies.}, number={0}, journal={Journal of Circadian Rhythms}, publisher={Ubiquity Press, Ltd.}, author={Roberts, Reade B and Thompson, Carol L and Lee, Daekee and Mankinen, Richard W and Sancar, Aziz and Threadgill, David W}, year={2006}, month={Nov}, pages={15} }
 @article{mrosovsky_redlin_roberts_threadgill_2005, title={Masking in Waved‐2 Mice: EGF Receptor Control of Locomotion Questioned}, volume={22}, ISSN={0742-0528 1525-6073}, url={http://dx.doi.org/10.1080/07420520500395086}, DOI={10.1080/07420520500395086}, abstractNote={It has been suggested that epidermal growth factors (EGF) are responsible for the inhibition of locomotion by light (i.e., masking) in nocturnal rodents (Kramer et al., ). The poor masking response of waved‐2 (Egfrwa2) mutant mice, with reduced EGF receptor activity, was adduced in support of this idea. In the present work, we studied the responses to light over a large range in illumination levels, in a variety of tests, with pulses of light and with ultradian light‐dark cycles in Egfrwa2 mutant mice. No evidence suggested that normal functioning of epidermal growth factor receptors was required, or even involved, in masking.}, number={6}, journal={Chronobiology International}, publisher={Informa UK Limited}, author={Mrosovsky, N. and Redlin, U. and Roberts, R. B. and Threadgill, D. W.}, year={2005}, month={Jan}, pages={963–974} }
 @inbook{roberts_threadgill_2005, title={THE MOUSE IN BIOMEDICAL RESEARCH}, ISBN={9781860945656 9781860947162}, url={http://dx.doi.org/10.1142/9781860947162_0015}, DOI={10.1142/9781860947162_0015}, booktitle={The Mouse in Animal Genetics and Breeding Research}, publisher={PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO.}, author={Roberts, R. B. and Threadgill, D. W.}, year={2005}, month={Jun}, pages={319–340} }
 @article{roberts_arteaga_threadgill_2004, title={Modeling the cancer patient with genetically engineered mice}, volume={5}, ISSN={1535-6108}, url={http://dx.doi.org/10.1016/s1535-6108(04)00032-7}, DOI={10.1016/s1535-6108(04)00032-7}, abstractNote={Current trends foretell the use of cancer treatments customized to each patient. Genetic and molecular profiling of tumors and an increasing number of molecule-targeted therapies contribute to making this a reality. However, as targets of anticancer therapies become specific proteins or pathways, unanticipated side effects may emerge. In addition, the chronic use of these treatments may contribute to the development of degenerative toxicity not predicted by short-term clinical trials. Here we review and propose how genetically engineered mouse models can serve as valuable tools to predict targeted therapy toxicity, as well as to identify allelic variants that predispose individuals to side effects.}, number={2}, journal={Cancer Cell}, publisher={Elsevier BV}, author={Roberts, Reade B and Arteaga, Carlos L and Threadgill, David W}, year={2004}, month={Feb}, pages={115–120} }
 @article{roberts_min_washington_olsen_settle_coffey_threadgill_2002, title={Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis}, volume={99}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.032678499}, DOI={10.1073/pnas.032678499}, abstractNote={
            We used the hypomorphic
            Egfr
            
              wa2
            
            allele to genetically examine the impact of impaired epidermal growth factor receptor (Egfr) signaling on the
            Apc
            
              Min
            
            mouse model of familial adenomatous polyposis. Transfer of the
            Apc
            
              Min
            
            allele onto a homozygous
            Egfr
            
              wa2
            
            background results in a 90% reduction in intestinal polyp number relative to
            Apc
            
              Min
            
            mice carrying a wild-type
            Egfr
            allele. This
            Egfr
            effect is potentially synergistic with the actions of the modifier-of-min (
            Mom1
            ) locus. Surprisingly, the size, expansion, and pathological progression of the polyps appear Egfr-independent. Histological examination of the ilea of younger animals revealed no differences in the number of microadenomas, the presumptive precursor lesions to gross intestinal polyps. Pharmacological inhibition with EKI-785, an Egfr tyrosine kinase inhibitor, produced similar results in the
            Apc
            
              Min
            
            model. These data suggest that normal Egfr activity is required for establishment of intestinal tumors in the
            Apc
            
              Min
            
            model between initiation and subsequent expansion of initiated tumors. The role of Egfr signaling during later stages of tumorigenesis was examined by using nude mice xenografts of two human colorectal cancer cell lines. Treatment with EKI-785 produced a dose-dependent reduction in tumor growth, suggesting that Egfr inhibitors may be useful for advanced colorectal cancer treatment.
          }, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Roberts, R. B. and Min, L. and Washington, M. K. and Olsen, S. J. and Settle, S. H. and Coffey, R. J. and Threadgill, D. W.}, year={2002}, month={Jan}, pages={1521–1526} }
 @article{strunk_roberts_2001, title={The 14th annual international mammalian genome society conference: A glimpse into the future of murine functional genomics}, volume={29}, ISSN={1526-954X 1526-968X}, url={http://dx.doi.org/10.1002/gene.1018}, DOI={10.1002/gene.1018}, abstractNote={The atmosphere of the 14 th annual International Mouse Genome Conference (IMGC) can only be described as one of anticipation and preparation for research in the murine postgenomic era. With the recent announcement of the completion of the human genome sequence and the continuing progress made in the genomics field, Science has declared sequenced genomes the break-through of the year 2000. Meanwhile, progress on sequencing the mouse genome is accelerating beyond expectations, and there is an intense focus in the mouse genetics community to ensure that the mouse model system will become a more potent research tool in the postgenomic era. IMGC 2000 was held November 6–9 in Narita, Japan, with over 300 people in attendance. At the end of the 4 days there was no doubt in any of the attendees’ minds that the availability of the murine genome sequence will revolutionize mouse-based research. There was also a clear understanding that sequence information is only as useful as the biological insight that can be mined from within its code; and this insight can only come with sequence accessibility and strong integration into a network of databases covering all known aspects of biology. Fortunately, many scientists and organizations have taken the dual tasks of genome management and biological analysis in some very inspiring directions. In the keynote address, Webster Cavenee (Director of the Ludwig Institute for Cancer Research, University of California, San Diego) established a paradigm for the discovery and characterization of genes involved in development and human disease. Following the discovery of the Forkhead-related ( FKHR ) transcription factor as a portion of an oncogenic translocation fusion found in human rhabdomyosarcoma, Dr. Cavenee was able to identify FKHR homologues in other species, and describe murine FkhrI function through a variety of ge-netic, biochemical, and cell biological experiments.}, number={4}, journal={genesis}, publisher={Wiley}, author={Strunk, Karen E. and Roberts, Reade Bruce}, year={2001}, pages={153–155} }