@article{grubbs_leach_su_petrisko_rosario_mahaffey_2013, title={New Components of Drosophila Leg Development Identified through Genome Wide Association Studies}, volume={8}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0060261}, abstractNote={The adult Drosophila melanogaster body develops from imaginal discs, groups of cells set-aside during embryogenesis and expanded in number during larval stages. Specification and development of Drosophila imaginal discs have been studied for many years as models of morphogenesis. These studies are often based on mutations with large developmental effects, mutations that are often lethal in embryos when homozygous. Such forward genetic screens can be limited by factors such as early lethality and genetic redundancy. To identify additional genes and genetic pathways involved in leg imaginal disc development, we employed a Genome Wide Association Study utilizing the natural genetic variation in leg proportionality found in the Drosophila Genetic Reference Panel fly lines. In addition to identifying genes already known to be involved in leg development, we identified several genes involved in pathways that had not previously been linked with leg development. Several of the genes appear to be involved in signaling activities, while others have no known roles at this time. Many of these uncharacterized genes are conserved in mammals, so we can now begin to place these genes into developmental contexts. Interestingly, we identified five genes which, when their function is reduced by RNAi, cause an antenna-to-leg transformation. Our results demonstrate the utility of this approach, integrating the tools of quantitative and molecular genetics to study developmental processes, and provide new insights into the pathways and networks involved in Drosophila leg development.}, number={4}, journal={PLOS ONE}, author={Grubbs, Nathaniel and Leach, Megan and Su, Xin and Petrisko, Tiffany and Rosario, Juan B. and Mahaffey, James W.}, year={2013}, month={Apr} }
 @misc{heffer_grubbs_mahaffey_pick_2013, title={The evolving role of the orphan nuclear receptor ftz-f1, a pair-rule segmentation gene}, volume={15}, ISSN={["1525-142X"]}, DOI={10.1111/ede.12050}, abstractNote={SUMMARY}, number={6}, journal={EVOLUTION & DEVELOPMENT}, author={Heffer, Alison and Grubbs, Nathaniel and Mahaffey, James and Pick, Leslie}, year={2013}, month={Nov}, pages={406–417} }
 @article{zhang_tsiatis_davidian_pieper_mahaffey_2011, title={Inference on treatment effects from a randomized clinical trial in the presence of premature treatment discontinuation: the SYNERGY trial}, volume={12}, ISSN={["1465-4644"]}, DOI={10.1093/biostatistics/kxq054}, abstractNote={The Superior Yield of the New Strategy of Enoxaparin, Revascularization, and GlYcoprotein IIb/IIIa inhibitors (SYNERGY) was a randomized, open-label, multicenter clinical trial comparing 2 anticoagulant drugs on the basis of time-to-event endpoints. In contrast to other studies of these agents, the primary, intent-to-treat analysis did not find evidence of a difference, leading to speculation that premature discontinuation of the study agents by some subjects may have attenuated the apparent treatment effect and thus to interest in inference on the difference in survival distributions were all subjects in the population to follow the assigned regimens, with no discontinuation. Such inference is often attempted via ad hoc analyses that are not based on a formal definition of this treatment effect. We use SYNERGY as a context in which to describe how this effect may be conceptualized and to present a statistical framework in which it may be precisely identified, which leads naturally to inferential methods based on inverse probability weighting.}, number={2}, journal={BIOSTATISTICS}, author={Zhang, Min and Tsiatis, Anastasios A. and Davidian, Marie and Pieper, Karen S. and Mahaffey, Kenneth W.}, year={2011}, month={Apr}, pages={258–269} }
 @article{dworkin_kennerly_tack_hutchinson_brown_mahaffey_gibson_2009, title={Genomic Consequences of Background Effects on scalloped Mutant Expressivity in the Wing of Drosophila melanogaster}, volume={181}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.108.096453}, abstractNote={Abstract}, number={3}, journal={GENETICS}, author={Dworkin, Ian and Kennerly, Erin and Tack, David and Hutchinson, Jennifer and Brown, Julie and Mahaffey, James and Gibson, Greg}, year={2009}, month={Mar}, pages={1065–1076} }
 @article{sanders_pate_mahaffey_2008, title={The drosophila gap gene giant has an anterior segment identity function mediated through disconnected and teashirt}, volume={179}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.107.084988}, abstractNote={Abstract}, number={1}, journal={GENETICS}, author={Sanders, Lisa R. and Pate, Mukund and Mahaffey, James W.}, year={2008}, month={May}, pages={441–453} }
 @article{patel_farzana_robertson_hutchinson_grubbs_shepherd_mahaffey_2007, title={The appendage role of insect disco genes and possible implications on the evolution of the maggot larval form}, volume={309}, ISSN={["0012-1606"]}, DOI={10.1016/j.ydbio.2007.06.017}, abstractNote={Though initially identified as necessary for neural migration, Disconnected and its partially redundant paralog, Disco-related, are required for proper head segment identity during Drosophila embryogenesis. Here, we present evidence that these genes are also required for proper ventral appendage development during development of the adult fly, where they specify medial to distal appendage development. Cells lacking the disco genes cannot contribute to the medial and distal portions of ventral appendages. Further, ectopic disco transforms dorsal appendages toward ventral fates; in wing discs, the medial and distal leg development pathways are activated. Interestingly, this appendage role is conserved in the red flour beetle, Tribolium (where legs develop during embryogenesis), yet in the beetle we found no evidence for a head segmentation role. The lack of an embryonic head specification role in Tribolium could be interpreted as a loss of the head segmentation function in Tribolium or gain of this function during evolution of flies. However, we suggest an alternative explanation. We propose that the disco genes always function as appendage factors, but their appendage nature is masked during Drosophila embryogenesis due to the reduction of limb fields in the maggot style Drosophila larva.}, number={1}, journal={DEVELOPMENTAL BIOLOGY}, author={Patel, Mukund and Farzana, Laila and Robertson, Lisa K. and Hutchinson, Jennifer and Grubbs, Nathaniel and Shepherd, Mark N. and Mahaffey, James W.}, year={2007}, month={Sep}, pages={56–69} }
 @article{mahaffey_dworkin_2006, title={Imaginal Discs, the Genetic and Cellular Logic of Pattern Formation. Lewis I Held, Jr. Cambridge University Press. 2005. 461 pages. ISBN 0 521 01835 8. Price £38. (paperback). (ISBN 0521 58445 0. Price £120. (hardback) published 2002)}, volume={87}, ISSN={0016-6723 1469-5073}, url={http://dx.doi.org/10.1017/S0016672306238254}, DOI={10.1017/S0016672306238254}, abstractNote={Imaginal Discs, the Genetic and Cellular Logic of Pattern Formation. Lewis I Held, Jr. Cambridge University Press. 2005. 461 pages. ISBN 0 521 01835 8. Price £38. (paperback). (ISBN 0521 58445 0. Price £120. (hardback) published 2002) - Volume 87 Issue 3}, number={3}, journal={Genetical Research}, publisher={Cambridge University Press (CUP)}, author={Mahaffey, James W. and Dworkin, Ian}, year={2006}, month={Jun}, pages={219–219} }
 @misc{mahaffey_2005, title={Assisting Hox proteins in controlling body form: are there new lessons from flies (and mammals)?}, volume={15}, ISSN={["0959-437X"]}, DOI={10.1016/j.gde.2005.06.009}, abstractNote={Hox proteins regulate specific sets of target genes to give rise to morphological distinctions along the anterior–posterior body axis of metazoans. Though they have high developmental specificity, Hox proteins have low DNA binding specificity, so how they select the appropriate target genes has remained enigmatic. There is general agreement that cofactors provide additional specificity, but a comprehensive model of Hox control of gene expression has not emerged. There is now evidence that a global network of zinc finger transcription factors contributes to patterning of the Drosophila embryo. These zinc finger proteins appear to establish fields in which certain Hox proteins can function. Though the nature of these fields is uncertain at this time, it is possible that these zinc finger proteins are Hox cofactors, providing additional specificity during Hox target-gene selection. Furthermore, these zinc finger proteins are conserved, as are aspects of their anterior–posterior expression, suggesting that their roles might be conserved, as well. Perhaps this layer in the genetic control of body patterning will help bridge some of the chasms that remain in our understanding of the genetic control of pattern formation.}, number={4}, journal={CURRENT OPINION IN GENETICS & DEVELOPMENT}, author={Mahaffey, JW}, year={2005}, month={Aug}, pages={422–429} }
 @article{robertson_bowling_mahaffey_imiolczyk_mahaffey_2004, title={An interactive network of zinc-finger proteins contributes to regionalization of the Drosophila embryo and establishes the domains of HOM-C protein function}, volume={131}, ISSN={["1477-9129"]}, DOI={10.1242/dev.01159}, abstractNote={During animal development, the HOM-C/HOX proteins direct axial patterning by regulating region-specific expression of downstream target genes. Though much is known about these pathways, significant questions remain regarding the mechanisms of specific target gene recognition and regulation, and the role of co-factors. From our studies of the gnathal and trunk-specification proteins Disconnected (DISCO) and Teashirt (TSH), respectively, we present evidence for a network of zinc-finger transcription factors that regionalize the Drosophila embryo. Not only do these proteins establish specific regions within the embryo, but their distribution also establishes where specific HOM-C proteins can function. In this manner, these factors function in parallel to the HOM-C proteins during axial specification. We also show that in tsh mutants, disco is expressed in the trunk segments, probably explaining the partial trunk to head transformation reported in these mutants, but more importantly demonstrating interactions between members of this regionalization network. We conclude that a combination of regionalizing factors, in concert with the HOM-C proteins,promotes the specification of individual segment identity.}, number={12}, journal={DEVELOPMENT}, author={Robertson, LK and Bowling, DB and Mahaffey, JP and Imiolczyk, B and Mahaffey, JW}, year={2004}, month={Jun}, pages={2781–2789} }
 @article{robertson_dey_campos_mahaffey_2002, title={Expression of the Drosophila gene disconnected using the UAS/GAL4 system}, volume={34}, ISSN={["1526-954X"]}, DOI={10.1002/gene.10123}, abstractNote={The Drosophila disconnected (disco) gene encodes a transcription factor containing two C2H2 zinc-fingers that functions in the development of both embryonic and adult structures. The disco gene was initially identified from a mutation in which adult photoreceptor axons fail to connect with their target cells in the larval optic lobe (Steller et al., 1987). The optic lobes of disco mutants are poorly developed and lack optic lobe neurons, including the lateral neurons. Abnormal circadian rhythmicity has been attributed to the absence or aberrant differentiation of these lateral neurons (Hardin et al., 1992; Helfrich-Forster et al., 1998). Additionally, disco mutants show defects in thoracic and abdominal sensory axon development (Glossop and Shepherd, 1998). More recently, disco was found to have a broader role in embryonic pattern formation, functioning as a cofactor for the Hox proteins Deformed (Dfd) and Sex Combs Reduced (Scr) in the gnathocephalic segments (mandibular, maxillary, and labial); this more extensive role was masked by the partially redundant gene, disco-related (disco-r) (Mahaffey et al., 2001). Lack of both Disco and Disco-r causes embryonic lethality and the absence of some larval mouth structures arising from the gnathocephalic segments. The disco gene is also expressed in the antennal and leg imaginal discs and likely has a role in the development of these structures (Lee et al., 1991). The disco gene is located in region 14B of the X chromosome and consists of two exons separated by a single intron. The first exon is untranslated and comprises the majority of the disco 5 UTR. The second exon contains the complete open reading frame (ORF) encoding the 568 amino acid protein. The two C2H2 zinc finger regions, defining the DNA binding domain, are located between amino acids 89 and 149 (Heilig et al., 1991). As tools for further study of Disco function, we generated three UAS-disco constructs—two encoding wildtype proteins and one producing an altered protein like that encoded by the disco null allele. The UAS-disco wild-type construct was generated by the sequential insertion of two disco fragments into the Drosophila transformation vector pUAST (Brand and Perrimon, 1993). A 1,270-bp BglII-XbaI fragment representing the majority of the disco ORF (a subclone from 542.2; Surdej et al., 1990) was inserted into BglII-XbaI digested pUAST. Next, a 473-bp fragment, with an artificial EcoRI site immediately upstream of the initiation codon, was obtained by an EcoRI-BglII digestion of a 1,276-bp PCR product generated with the following primers: Forward primer, 5 GGA TCC GAATTC ATG GAG CAC ATA ATG 3 ; Reverse Primer, 5 ATG TAG GCA CTG TCG CTA TCC 3 . This fragment was inserted into the EcoRI-BglII sites of the initial BglII-XbaI pUAST construct. The final construct includes a 1,743-bp EcoRI-XbaI insert encoding the entire disco ORF with some 3 UTR. The second wild-type construct (further referred to as UAS-disco) and the mutant construct (further referred to as UAS-disco) were generated by PCR amplification of genomic DNA. A 1,704-bp fragment containing the complete disco ORF was generated using primers containing EcoRI sites: Forward primer, 5 CCC ACC ACA GAATTC ATG GAG CAC 3 ; Reverse Primer, 5 CCA TGG ATC GAATTC TGG ACA TTA 3 . After EcoRI digestion, the resulting PCR product was inserted into an EcoRI digested pUAST. For the UAS-disco construct, Oregon R genomic DNA was used as a template, while homozygous disco genomic DNA was used as a template for the mutant UAS-disco construct. This form of the protein contains a single amino acid change— Cysteine 127 is substituted with a Serine—which disrupts the first zinc finger. Prior analysis indicated that this mutant form of the Disco protein is nonfunctional (Heilig et al., 1991; Mahaffey et al., 2001). The sequence and reading frame of all constructs were verified by DNA sequence analysis. Integration of UAS-disco constructs into the Drosophila genome was carried out using P-element-mediated germ-line transformation essentially as described by Rubin and Spradling (1982). Two UAS-disco lines were obtained—a heterozygous line carrying UAS-disco on the second chromosome balanced over CyO (UAS-disco(II)), and a homozygous line with the insert on the}, number={1-2}, journal={GENESIS}, author={Robertson, LK and Dey, BK and Campos, AR and Mahaffey, JW}, year={2002}, pages={103–106} }
 @article{mahaffey_griswold_cao_2001, title={The drosophila genes disconnected and disco-related are redundant with respect to larval head development and accumulation of mRNAs from deformed target genes}, volume={157}, number={1}, journal={Genetics}, author={Mahaffey, J. W. and Griswold, C. M. and Cao, Q. M.}, year={2001}, pages={225–236} }
 @article{pederson_lafollette_gross_veraksa_mcginnis_mahaffey_2000, title={Regulation by homeoproteins: A comparison of deformed- responsive elements}, volume={156}, number={2}, journal={Genetics}, author={Pederson, J. A. and LaFollette, J. W. and Gross, C. and Veraksa, A. and McGinnis, W. and Mahaffey, J. W.}, year={2000}, pages={677–686} }
 @article{brown_mahaffey_lorenzen_denell_mahaffey_1999, title={Using RNAi to investigate orthologous homeotic gene function during development of distantly related insects}, volume={1}, ISSN={1520-541X 1525-142X}, url={http://dx.doi.org/10.1046/j.1525-142x.1999.99013.x}, DOI={10.1046/j.1525-142x.1999.99013.x}, abstractNote={Gene product distribution is often used to infer developmental similarities and differences in animals with evolutionarily diverse body plans. However, to address commonalties of developmental mechanisms, what is really needed is a method to assess and compare gene function in divergent organisms. This requires mutations eliminating gene function. Such mutations are often difficult to obtain, even in organisms amenable to genetic analysis. To address this issue we have investigated the use of double‐stranded RNA interference to phenocopy null mutations. We show that RNA interference can be used to phenocopy mutations of the Deformed orthologues in Drosophila and Tribolium. We discuss the possible use of this technique for comparisons of developmental mechanisms in organisms with differing ontogenies.}, number={1}, journal={Evolution and Development}, publisher={Wiley}, author={Brown, Susan J. and Mahaffey, James P. and Lorenzen, Marce D. and Denell, Robin E. and Mahaffey, James W.}, year={1999}, month={Jul}, pages={11–15} }
 @article{fyrberg_becker_barthmaier_mahaffey_fyrberg_1998, title={A family of Drosophila genes encoding quaking-related maxi-KH domains}, volume={36}, ISSN={["0006-2928"]}, DOI={10.1023/A:1018700202971}, abstractNote={We recently identified a Drosophila gene, wings held out (who), that specifies a STAR (signal transduction and RNA activation) protein expressed within mesoderm and muscles. Genetic evidence suggests that WHO regulates muscle development and function in response to steroid hormone titer. who is related to the mouse quacking gene, essential for embryogenesis and neural myelination, and gld-1, a nematode tumor suppressor gene necessary for oocyte differentiation, both of which contain RNA binding "maxi-KH" domains presumed to link RNA metabolism to cell signaling. To initiate a broader study of Drosophila WHO-related proteins we used degenerate primers encoding peptides unique to maxi-KH domains to amplify the corresponding genes. We recovered nine genes, all specifying single maxi-KH domain proteins having tripartite regions of similarity that extend over 200 amino acids. One is located within the 54D chromosome subdivision, and one within 58C, while the remaining seven are within the 58E subdivision. At least four of these STAR proteins are expressed in a general manner, suggesting that maxi-KH domains are employed widely in Drosophila.}, number={1-2}, journal={BIOCHEMICAL GENETICS}, author={Fyrberg, C and Becker, J and Barthmaier, P and Mahaffey, J and Fyrberg, E}, year={1998}, month={Feb}, pages={51–64} }
 @article{fyrberg_becker_barthmaier_mahaffey_fyrberg_1997, title={A Drosophila muscle-specific gene related to the mouse quaking locus}, volume={197}, ISSN={["0378-1119"]}, DOI={10.1016/S0378-1119(97)00278-3}, abstractNote={We have characterized a novel muscle-specific gene of Drosophila melanogaster, defined by enhancer trap strain 24B of Brand and Perrimon (1993). We show that transcripts of the gene accumulate within presumptive mesoderm and persist within developing muscles, strongly suggesting that the encoded protein is involved in muscle cell determination and differentiation. cDNA sequences reveal that the Drosophila protein is similar to quaking (64% identity over 210 amino acids), a protein essential for mouse embryogenesis, and gld-1 (53% identity over 162 amino acids) a germ-line-specific tumor suppressing protein of the nematode, Caenorhabditis elegans. We demonstrate that the Drosophila gene resides within the 93F chromosome subdivision, and describe its physical map. Finally, we have used the gene, which we have named quaking-related 93F (qkr93F), to identify a family of closely related KH domains.}, number={1-2}, journal={GENE}, author={Fyrberg, C and Becker, J and Barthmaier, P and Mahaffey, J and Fyrberg, E}, year={1997}, month={Sep}, pages={315–323} }