@article{zahn_james-zorn_ponferrada_adams_grzymkowski_buchholz_nascone-yoder_horb_moody_vize_et al._2022, title={Normal Table of Xenopus development: a new graphical resource}, volume={149}, ISSN={["1477-9129"]}, DOI={10.1242/dev.200356}, abstractNote={Normal tables of development are essential for studies of embryogenesis, serving as an important resource for model organisms, including the frog Xenopus laevis. Xenopus has long been used to study developmental and cell biology, and is an increasingly important model for human birth defects and disease, genomics, proteomics and toxicology. Scientists utilize Nieuwkoop and Faber's classic 'Normal Table of Xenopus laevis (Daudin)' and accompanying illustrations to enable experimental reproducibility and reuse the illustrations in new publications and teaching. However, it is no longer possible to obtain permission for these copyrighted illustrations. We present 133 new, high-quality illustrations of X. laevis development from fertilization to metamorphosis, with additional views that were not available in the original collection. All the images are available on Xenbase, the Xenopus knowledgebase (http://www.xenbase.org/entry/zahn.do), for download and reuse under an attributable, non-commercial creative commons license. Additionally, we have compiled a 'Landmarks Table' of key morphological features and marker gene expression that can be used to distinguish stages quickly and reliably (https://www.xenbase.org/entry/landmarks-table.do). This new open-access resource will facilitate Xenopus research and teaching in the decades to come.}, number={14}, journal={DEVELOPMENT}, author={Zahn, Natalya and James-Zorn, Christina and Ponferrada, Virgilio G. and Adams, Dany S. and Grzymkowski, Julia and Buchholz, Daniel R. and Nascone-Yoder, Nanette M. and Horb, Marko and Moody, Sally A. and Vize, Peter D. and et al.}, year={2022}, month={Jul} }
 @article{wyatt_amin_bagley_wcisel_dush_yoder_nascone-yoder_2021, title={Single-minded 2 is required for left-right asymmetric stomach morphogenesis}, volume={148}, ISSN={["1477-9129"]}, DOI={10.1242/dev.199265}, abstractNote={The morphogenesis of left-right (LR) asymmetry is a critical phase of organogenesis. In the digestive tract, the development of anatomical asymmetry is first evident in the leftward curvature of the stomach. To elucidate the molecular events that shape this archetypal laterality, we performed transcriptome analyses of the left versus right sides of the developing stomach in frog embryos. Besides the known LR gene pitx2, the only gene found to be expressed asymmetrically throughout all stages of curvature was single-minded2 (sim2), a Down Syndrome-related transcription factor and homolog of a Drosophila gene (sim) required for LR asymmetric looping of the fly gut. We demonstrate that sim2 functions downstream of LR patterning cues to regulate key cellular properties and behaviors in the left stomach epithelium that drive asymmetric curvature. Our results reveal unexpected convergent cooption of single-minded genes during the evolution of LR asymmetric morphogenesis, and have implications for dose-dependent roles of laterality factors in non-laterality-related birth defects.}, number={17}, journal={DEVELOPMENT}, author={Wyatt, Brent H. and Amin, Nirav M. and Bagley, Kristen and Wcisel, Dustin and Dush, Michael K. and Yoder, Jeffrey A. and Nascone-Yoder, Nanette M.}, year={2021}, month={Sep} }
 @misc{grzymkowski_wyatt_nascone-yoder_2020, title={The twists and turns of left-right asymmetric gut morphogenesis}, volume={147}, ISSN={["1477-9129"]}, DOI={10.1242/dev.187583}, abstractNote={ABSTRACT Many organs develop left-right asymmetric shapes and positions that are crucial for normal function. Indeed, anomalous laterality is associated with multiple severe birth defects. Although the events that initially orient the left-right body axis are beginning to be understood, the mechanisms that shape the asymmetries of individual organs remain less clear. Here, we summarize new evidence challenging century-old ideas about the development of stomach and intestine laterality. We compare classical and contemporary models of asymmetric gut morphogenesis and highlight key unanswered questions for future investigation.}, number={19}, journal={DEVELOPMENT}, author={Grzymkowski, Julia and Wyatt, Brent and Nascone-Yoder, Nanette}, year={2020}, month={Oct} }
 @article{jenkins_almli_pangilinan_chong_blue_shapira_white_mcgoldrick_smith_mullikin_et al._2019, title={Exome sequencing of family trios from the National Birth Defects Prevention Study: Tapping into a rich resource of genetic and environmental data}, volume={111}, ISSN={["2472-1727"]}, DOI={10.1002/bdr2.1554}, abstractNote={Background The National Birth Defects Prevention Study (NBDPS) is a multisite, population-based, case–control study of genetic and nongenetic risk factors for major structural birth defects. Eligible women had a pregnancy affected by a birth defect or a liveborn child without a birth defect between 1997 and 2011. They were invited to complete a telephone interview to collect pregnancy exposure data and were mailed buccal cell collection kits to collect specimens from themselves, their child (if living), and their child's father. Over 23,000 families representing more than 30 major structural birth defects provided DNA specimens. Methods To evaluate their utility for exome sequencing (ES), specimens from 20 children with colonic atresia were studied. Evaluations were conducted on specimens collected using cytobrushes stored and transported in open versus closed packaging, on native genomic DNA (gDNA) versus whole genome amplified (WGA) products and on a library preparation protocol adapted to low amounts of DNA. Results The DNA extracted from brushes in open packaging yielded higher quality sequence data than DNA from brushes in closed packaging. Quality metrics of sequenced gDNA were consistently higher than metrics from corresponding WGA products and were consistently high when using a low input protocol. Conclusions This proof-of-principle study established conditions under which ES can be applied to NBDPS specimens. Successful sequencing of exomes from well-characterized NBDPS families indicated that this unique collection can be used to investigate the roles of genetic variation and gene–environment interaction effects in birth defect etiologies, providing a valuable resource for birth defect researchers.}, number={20}, journal={BIRTH DEFECTS RESEARCH}, author={Jenkins, Mary M. and Almli, Lynn M. and Pangilinan, Faith and Chong, Jessica X. and Blue, Elizabeth E. and Shapira, Stuart K. and White, Janson and McGoldrick, Daniel and Smith, Joshua D. and Mullikin, James C. and et al.}, year={2019}, month={Dec}, pages={1618–1632} }
 @article{dush_nascone-yoder_2019, title={Vangl2 coordinates cell rearrangements during gut elongation}, volume={248}, ISSN={["1097-0177"]}, DOI={10.1002/dvdy.61}, abstractNote={Background The embryonic gut tube undergoes extensive lengthening to generate the surface area required for nutrient absorption across the digestive epithelium. In Xenopus, narrowing and elongation of the tube is driven by radial rearrangements of its core of endoderm cells, a process that concomitantly opens the gut lumen and facilitates epithelial morphogenesis. How endoderm rearrangements are properly oriented and coordinated to achieve this complex morphogenetic outcome is unknown. Results We find that, prior to gut elongation, the core Wnt/PCP component Vangl2 becomes enriched at both the anterior and apical aspects of individual endoderm cells. In Vangl2-depleted guts, the cells remain unpolarized, down-regulate cell-cell adhesion proteins, and, consequently, fail to rearrange, leading to a short gut with an occluded lumen and undifferentiated epithelium. In contrast, endoderm cells with ectopic Vangl2 protein acquire abnormal polarity and adhesive contacts. As a result, endoderm cells also fail to rearrange properly and undergo ectopic differentiation, resulting in guts with multiple torturous lumens, irregular epithelial architecture, and variable intestinal topologies. Conclusions Asymmetrical enrichment of Vangl2 in individual gut endoderm cells orients polarity and adhesion during radial rearrangements, coordinating digestive epithelial morphogenesis and lumen formation with gut tube elongation.}, number={7}, journal={DEVELOPMENTAL DYNAMICS}, author={Dush, Michael K. and Nascone-Yoder, Nanette M.}, year={2019}, month={Jul}, pages={569–582} }
 @article{womble_amin_nascone-yoder_2018, title={The left-right asymmetry of liver lobation is generated by Pitx2c-mediated asymmetries in the hepatic diverticulum}, volume={439}, ISSN={["1095-564X"]}, DOI={10.1016/j.ydbio.2018.04.021}, abstractNote={Internal organs exhibit left-right asymmetric sizes, shapes and anatomical positions, but how these different lateralities develop is poorly understood. Here we use the experimentally tractable Xenopus model to uncover the morphogenetic events that drive the left-right asymmetrical lobation of the liver. On the right side of the early hepatic diverticulum, endoderm cells become columnar and apically constricted, forming an expanded epithelial surface and, ultimately, an enlarged right liver lobe. In contrast, the cells on the left side become rounder, and rearrange into a compact, stratified architecture that produces a smaller left lobe. Side-specific gain- and loss-of-function studies reveal that asymmetric expression of the left-right determinant Pitx2c elicits distinct epithelial morphogenesis events in the left side of the diverticulum. Surprisingly, the cellular events induced by Pitx2c during liver development are opposite those induced in other digestive organs, suggesting divergent cellular mechanisms underlie the formation of different lateralities.}, number={2}, journal={DEVELOPMENTAL BIOLOGY}, author={Womble, Mandy and Amin, Nirav M. and Nascone-Yoder, Nanette}, year={2018}, month={Jul}, pages={80–91} }
 @article{pickett_dush_nascone-yoder_2017, title={Acetylcholinesterase plays a non-neuronal, non-esterase role in organogenesis}, volume={144}, ISSN={["1477-9129"]}, DOI={10.1242/dev.149831}, abstractNote={Acetylcholinesterase (AChE) is crucial for degrading acetylcholine at cholinergic synapses. In vitro studies suggest that, in addition to its role in nervous signaling, AChE can also modulate non-neuronal cell properties, although it remains controversial whether AChE functions in this capacity in vivo. Here, we show that AChE plays an essential non-classical role in vertebrate gut morphogenesis. Exposure of Xenopus embryos to AChE-inhibiting chemicals results in severe defects in intestinal development. Tissue-targeted loss of function assays (via microinjection of antisense morpholino or CRISPR-Cas9) confirm that AChE is specifically required in the gut endoderm tissue, a non-neuronal cell population, where it mediates adhesion to fibronectin and regulates cell rearrangement events that drive gut lengthening and digestive epithelial morphogenesis. Notably, the classical esterase activity of AChE is dispensable for this activity. As AChE is deeply conserved, widely expressed outside of the nervous system, and the target of many environmental chemicals, these results have broad-reaching implications for development and toxicology.}, number={15}, journal={DEVELOPMENT}, author={Pickett, Melissa A. and Dush, Michael K. and Nascone-Yoder, Nanette M.}, year={2017}, month={Aug}, pages={2764–2770} }
 @article{davis_amin_johnson_bagley_ghashghaei_nascone-yoder_2017, title={Stomach curvature is generated by left-right asymmetric gut morphogenesis}, volume={144}, ISSN={["1477-9129"]}, DOI={10.1242/dev.143701}, abstractNote={Left-right (LR) asymmetry is a fundamental feature of internal anatomy, yet the emergence of morphological asymmetry remains one of the least understood phases of organogenesis. Asymmetric rotation of the intestine is directed by forces outside of the gut, but the morphogenetic events that generate anatomical asymmetry in other regions of the digestive tract remain unknown. Here we show that the mechanisms that drive the curvature of the stomach are intrinsic to the gut tube itself. The left wall of the primitive stomach expands more than the right wall, as the left epithelium becomes more polarized and undergoes radial rearrangement. These asymmetries exist across species, and are dependent on LR patterning genes, including FoxJ1, Nodal and Pitx2. Our findings have implications for how LR patterning manifests distinct types of morphological asymmetries in different contexts.}, number={8}, journal={DEVELOPMENT}, author={Davis, Adam and Amin, Nirav M. and Johnson, Caroline and Bagley, Kristen and Ghashghaei, H. Troy and Nascone-Yoder, Nanette}, year={2017}, month={Apr}, pages={1477–1483} }
 @misc{womble_pickett_nascone-yoder_2016, title={Frogs as integrative models for understanding digestive organ development and evolution}, volume={51}, ISSN={["1084-9521"]}, DOI={10.1016/j.semcdb.2016.02.001}, abstractNote={The digestive system comprises numerous cells, tissues and organs that are essential for the proper assimilation of nutrients and energy. Many aspects of digestive organ function are highly conserved among vertebrates, yet the final anatomical configuration of the gut varies widely between species, especially those with different diets. Improved understanding of the complex molecular and cellular events that orchestrate digestive organ development is pertinent to many areas of biology and medicine, including the regeneration or replacement of diseased organs, the etiology of digestive organ birth defects, and the evolution of specialized features of digestive anatomy. In this review, we highlight specific examples of how investigations using Xenopus laevis frog embryos have revealed insight into the molecular and cellular dynamics of digestive organ patterning and morphogenesis that would have been difficult to obtain in other animal models. Additionally, we discuss recent studies of gut development in non-model frog species with unique feeding strategies, such as Lepidobatrachus laevis and Eleutherodactylous coqui, which are beginning to provide glimpses of the evolutionary mechanisms that may generate morphological variation in the digestive tract. The unparalleled experimental versatility of frog embryos make them excellent, integrative models for studying digestive organ development across multiple disciplines.}, journal={SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY}, author={Womble, Mandy and Pickett, Melissa and Nascone-Yoder, Nanette}, year={2016}, month={Mar}, pages={92–105} }
 @article{amin_womble_ledon-rettig_hull_dickinson_nascone-yoder_2015, title={Budgett's frog (Lepidobatrachus laevis): A new amphibian embryo for developmental biology}, volume={405}, ISSN={["1095-564X"]}, DOI={10.1016/j.ydbio.2015.06.007}, abstractNote={The large size and rapid development of amphibian embryos has facilitated ground-breaking discoveries in developmental biology. Here, we describe the embryogenesis of the Budgett's frog (Lepidobatrachus laevis), an unusual species with eggs that are over twice the diameter of laboratory Xenopus, and embryos that can tolerate higher temperatures to develop into a tadpole four times more rapidly. In addition to detailing their early development, we demonstrate that, like Xenopus, these embryos are amenable to explant culture assays and can express exogenous transcripts in a tissue-specific manner. Moreover, the steep developmental trajectory and large scale of Lepidobatrachus make it exceptionally well-suited for morphogenesis research. For example, the developing organs of the Budgett's frog are massive compared to those of most model species, and are composed of larger individual cells, thereby affording increased subcellular resolution of early vertebrate organogenesis. Furthermore, we found that complete limb regeneration, which typically requires months to achieve in most vertebrate models, occurs in a matter of days in the Budgett's tadpole, which substantially accelerates the pace of experimentation. Thus, the unusual combination of the greater size and speed of the Budgett's frog model provides inimitable advantages for developmental studies-and a novel inroad to address the mechanisms of spatiotemporal scaling during evolution.}, number={2}, journal={DEVELOPMENTAL BIOLOGY}, author={Amin, Nirav M. and Womble, Mandy and Ledon-Rettig, Cristina and Hull, Margaret and Dickinson, Amanda and Nascone-Yoder, Nanette}, year={2015}, month={Sep}, pages={291–303} }
 @article{stern_white_lehmkuhl_reina-doreste_ferguson_nascone-yoder_meurs_2014, title={A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs}, volume={133}, ISSN={0340-6717 1432-1203}, url={http://dx.doi.org/10.1007/s00439-014-1454-0}, DOI={10.1007/s00439-014-1454-0}, abstractNote={Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We hypothesized that SAS in Newfoundlands is inherited in an autosomal dominant pattern and caused by a single genetic variant. We studied 93 prospectively recruited Newfoundland dogs, and 180 control dogs of 30 breeds. By providing cardiac screening evaluations for Newfoundlands we conducted a pedigree evaluation, genome-wide association study and RNA sequence analysis to identify a proposed pattern of inheritance and genetic loci associated with the development of SAS. We identified a three-nucleotide exonic insertion in phosphatidylinositol-binding clathrin assembly protein (PICALM) that is associated with the development of SAS in Newfoundlands. Pedigree evaluation best supported an autosomal dominant pattern of inheritance and provided evidence that equivocally affected individuals may pass on SAS in their progeny. Immunohistochemistry demonstrated the presence of PICALM in the canine myocardium and area of the subvalvular ridge. Additionally, small molecule inhibition of clathrin-mediated endocytosis resulted in developmental abnormalities within the outflow tract (OFT) of Xenopus laevis embryos. The ability to test for presence of this PICALM insertion may impact dog-breeding decisions and facilitate reduction of SAS disease prevalence in Newfoundland dogs. Understanding the role of PICALM in OFT development may aid in future molecular and genetic investigations into other congenital heart defects of various species.}, number={9}, journal={Human Genetics}, publisher={Springer Nature}, author={Stern, Joshua A. and White, Stephen N. and Lehmkuhl, Linda B. and Reina-Doreste, Yamir and Ferguson, Jordan L. and Nascone-Yoder, Nanette M. and Meurs, Kathryn M.}, year={2014}, month={Jun}, pages={1139–1148} }
 @article{ross_marcot_betteridge_nascone-yoder_bailey_sears_2013, title={CONSTRAINTS ON MAMMALIAN FORELIMB DEVELOPMENT: INSIGHTS FROM DEVELOPMENTAL DISPARITY}, volume={67}, ISSN={0014-3820}, url={http://dx.doi.org/10.1111/evo.12204}, DOI={10.1111/evo.12204}, abstractNote={Tetrapod limb development has been studied extensively for decades, yet the strength and role of developmental constraints in this process remains unresolved. Mammals exhibit a particularly wide array of limb morphologies associated with various locomotion modes and behaviors, providing a useful system for identifying periods of developmental constraint and conserved developmental mechanisms or morphologies. In this study, landmark-based geometric morphometrics are used to investigate levels and patterns of morphological diversity (disparity) among the developing forelimbs of four mammals with diverse limb morphologies: mice, opossums, horses, and pigs. Results indicate that disparity among the forelimbs of these species slightly decreases or stays the same from the appearance of the limb ridge to the bud stage, and increases dramatically from the paddle through tissue regression stages. Heterochrony exhibited by the precocial opossum limb was not found to drive these patterns of morphological disparity, suggesting that the low disparity of the middle stages of limb development (e.g., paddle stage) is driven by processes operating within the limb and is likely not a result of embryo-wide constraint.}, number={12}, journal={Evolution}, publisher={Wiley}, author={Ross, Darcy and Marcot, Jonathan D. and Betteridge, Keith J. and Nascone-Yoder, Nanette and Bailey, C. Scott and Sears, Karen E.}, year={2013}, month={Sep}, pages={3645–3652} }
 @article{bloom_ledon-rettig_infante_everly_hanken_nascone-yoder_2013, title={Developmental origins of a novel gut morphology in frogs}, volume={15}, ISSN={["1525-142X"]}, DOI={10.1111/ede.12035}, abstractNote={Phenotypic variation is a prerequisite for evolution by natural selection, yet the processes that give rise to the novel morphologies upon which selection acts are poorly understood. We employed a chemical genetic screen to identify developmental changes capable of generating ecologically relevant morphological variation as observed among extant species. Specifically, we assayed for exogenously applied small molecules capable of transforming the ancestral larval foregut of the herbivorous Xenopus laevis to resemble the derived larval foregut of the carnivorous Lepidobatrachus laevis. Appropriately, the small molecules that demonstrate this capacity modulate conserved morphogenetic pathways involved in gut development, including downregulation of retinoic acid (RA) signaling. Identical manipulation of RA signaling in a species that is more closely related to Lepidobatrachus, Ceratophrys cranwelli, yielded even more similar transformations, corroborating the relevance of RA signaling variation in interspecific morphological change. Finally, we were able to recover the ancestral gut phenotype in Lepidobatrachus by performing a reverse chemical manipulation to upregulate RA signaling, providing strong evidence that modifications to this specific pathway promoted the emergence of a lineage-specific phenotypic novelty. Interestingly, our screen also revealed pathways that have not yet been implicated in early gut morphogenesis, such as thyroid hormone signaling. In general, the chemical genetic screen may be a valuable tool for identifying developmental mechanisms that underlie ecologically and evolutionarily relevant phenotypic variation.}, number={3}, journal={EVOLUTION & DEVELOPMENT}, author={Bloom, Stephanie and Ledon-Rettig, Cris and Infante, Carlos and Everly, Anne and Hanken, James and Nascone-Yoder, Nanette}, year={2013}, month={May}, pages={213–223} }
 @article{dush_nascone-yoder_2013, title={Jun N-terminal kinase maintains tissue integrity during cell rearrangement in the gut}, volume={140}, ISSN={["0950-1991"]}, DOI={10.1242/dev.086850}, abstractNote={Tissue elongation is a fundamental morphogenetic process that generates the proper anatomical topology of the body plan and vital organs. In many elongating embryonic structures, tissue lengthening is driven by Rho family GTPase-mediated cell rearrangement. During this dynamic process, the mechanisms that modulate intercellular adhesion to allow individual cells to change position without compromising structural integrity are not well understood. In vertebrates, Jun N-terminal kinase (JNK) is also required for tissue elongation, but the precise cellular role of JNK in this context has remained elusive. Here, we show that JNK activity is indispensable for the rearrangement of endoderm cells that underlies the elongation of the Xenopus gut tube. Whereas Rho kinase is necessary to induce cell intercalation and remodel adhesive contacts, we have found that JNK is required to maintain cell-cell adhesion and establish parallel microtubule arrays; without JNK activity, the reorganizing endoderm dissociates. Depleting polymerized microtubules phenocopies this effect of JNK inhibition on endoderm morphogenesis, consistent with a model in which JNK regulates microtubule architecture to preserve adhesive contacts between rearranging gut cells. Thus, in contrast to Rho kinase, which generates actomyosin-based tension and cell movement, JNK signaling is required to establish microtubule stability and maintain tissue cohesion; both factors are required to achieve proper cell rearrangement and gut extension. This model of gut elongation has implications not only for the etiology of digestive tract defects, but sheds new light on the means by which intra- and intercellular forces are balanced to promote topological change, while preserving structural integrity, in numerous morphogenetic contexts.}, number={7}, journal={DEVELOPMENT}, author={Dush, Michael K. and Nascone-Yoder, Nanette M.}, year={2013}, month={Apr}, pages={1457–1466} }
 @article{morckel_lusic_farzana_yoder_deiters_nascone-yoder_2011, title={A photoactivatable small-molecule inhibitor for light-controlled spatiotemporal regulation of Rho kinase in live embryos}, volume={139}, ISSN={0950-1991 1477-9129}, url={http://dx.doi.org/10.1242/dev.072165}, DOI={10.1242/dev.072165}, abstractNote={To uncover the molecular mechanisms of embryonic development, the ideal loss-of-function strategy would be capable of targeting specific regions of the living embryo with both temporal and spatial precision. To this end, we have developed a novel pharmacological agent that can be light activated to achieve spatiotemporally limited inhibition of Rho kinase activity in vivo. A new photolabile caging group, 6-nitropiperonyloxymethyl (NPOM), was installed on a small-molecule inhibitor of Rho kinase, Rockout, to generate a ‘caged Rockout’ derivative. Complementary biochemical, cellular, molecular and morphogenetic assays in both mammalian cell culture and Xenopus laevis embryos validate that the inhibitory activity of the caged compound is dependent on exposure to light. Conveniently, this unique reagent retains many of the practical advantages of conventional small-molecule inhibitors, including delivery by simple diffusion in the growth medium and concentration-dependent tuneability, but can be locally activated by decaging with standard instrumentation. Application of this novel tool to the spatially heterogeneous problem of embryonic left-right asymmetry revealed a differential requirement for Rho signaling on the left and right sides of the primitive gut tube, yielding new insight into the molecular mechanisms that generate asymmetric organ morphology. As many aromatic/heterocyclic small-molecule inhibitors are amenable to installation of this caging group, our results indicate that photocaging pharmacological inhibitors might be a generalizable technique for engendering convenient loss-of-function reagents with great potential for wide application in developmental biology.}, number={2}, journal={Development}, publisher={The Company of Biologists}, author={Morckel, A. R. and Lusic, H. and Farzana, L. and Yoder, J. A. and Deiters, A. and Nascone-Yoder, N. M.}, year={2011}, month={Dec}, pages={437–442} }
 @article{dush_mciver_parr_young_fisher_newman_sannes_hauck_deiters_nascone-yoder_2011, title={Heterotaxin: A TGF-beta Signaling Inhibitor Identified in a Multi-Phenotype Profiling Screen in Xenopus Embryos}, volume={18}, ISSN={["1879-1301"]}, DOI={10.1016/j.chembiol.2010.12.008}, abstractNote={Disruptions of anatomical left-right asymmetry result in life-threatening heterotaxic birth defects in vital organs. We performed a small molecule screen for left-right asymmetry phenotypes in Xenopus embryos and discovered a pyridine analog, heterotaxin, which disrupts both cardiovascular and digestive organ laterality and inhibits TGF-β-dependent left-right asymmetric gene expression. Heterotaxin analogs also perturb vascular development, melanogenesis, cell migration, and adhesion, and indirectly inhibit the phosphorylation of an intracellular mediator of TGF-β signaling. This combined phenotypic profile identifies these compounds as a class of TGF-β signaling inhibitors. Notably, heterotaxin analogs also possess highly desirable antitumor properties, inhibiting epithelial-mesenchymal transition, angiogenesis, and tumor cell proliferation in mammalian systems. Our results suggest that assessing multiple organ, tissue, cellular, and molecular parameters in a whole organism context is a valuable strategy for identifying the mechanism of action of bioactive compounds.}, number={2}, journal={CHEMISTRY & BIOLOGY}, author={Dush, Michael K. and McIver, Andrew L. and Parr, Meredith A. and Young, Douglas D. and Fisher, Julie and Newman, Donna R. and Sannes, Philip L. and Hauck, Marlene L. and Deiters, Alexander and Nascone-Yoder, Nanette}, year={2011}, month={Feb}, pages={252–263} }
 @article{dush_nascone-yoder_2011, title={Rac/JNK/dub regulates intercellular adhesive dynamics during gut morphogenesis}, volume={356}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2011.05.136}, DOI={10.1016/j.ydbio.2011.05.136}, number={1}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Dush, Michael and Nascone-Yoder, Nanette M.}, year={2011}, month={Aug}, pages={141} }
 @article{chung_nascone-yoder_grover_drysdale_wallingford_2010, title={Direct activation of Shroom3 transcription by Pitx proteins drives epithelial morphogenesis in the developing gut}, volume={137}, ISSN={["1477-9129"]}, DOI={10.1242/dev.044610}, abstractNote={Individual cell shape changes are essential for epithelial morphogenesis. A transcriptional network for epithelial cell shape change is emerging in Drosophila, but this area remains largely unexplored in vertebrates. The distinction is important as so far, key downstream effectors of cell shape change in Drosophila appear not to be conserved. Rather, Shroom3 has emerged as a central effector of epithelial morphogenesis in vertebrates, driving both actin- and microtubule-based cell shape changes. To date, the morphogenetic role of Shroom3 has been explored only in the neural epithelium, so the broad expression of this gene raises two important questions: what are the requirements for Shroom3 in non-neural tissues and what factors control Shroom3 transcription? Here, we show in Xenopus that Shroom3 is essential for cell shape changes and morphogenesis in the developing vertebrate gut and that Shroom3 transcription in the gut requires the Pitx1 transcription factor. Moreover, we show that Pitx proteins directly activate Shroom3 transcription, and we identify Pitx-responsive regulatory elements in the genomic DNA upstream of Shroom3. Finally, we show that ectopic expression of Pitx proteins is sufficient to induce Shroom3-dependent cytoskeletal reorganization and epithelial cell shape change. These data demonstrate new breadth to the requirements for Shroom3 in morphogenesis, and they also provide a cell-biological basis for the role of Pitx transcription factors in morphogenesis. More generally, these results provide a foundation for deciphering the transcriptional network that underlies epithelial cell shape change in developing vertebrates.}, number={8}, journal={DEVELOPMENT}, author={Chung, Mei-I and Nascone-Yoder, Nanette M. and Grover, Stephanie A. and Drysdale, Thomas A. and Wallingford, John B.}, year={2010}, month={Apr}, pages={1339–1349} }
 @article{nascone-yoder_dush_mciver_parr_young_fisher_hauck_deiters_2010, title={Heterotaxin: A novel TGF-beta signaling inhibitor identified in a multi-phenotype profiling screen in Xenopus embryos}, volume={344}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2010.05.483}, DOI={10.1016/j.ydbio.2010.05.483}, number={1}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Nascone-Yoder, Nanette M. and Dush, Michael and McIver, Andrew and Parr, Meredith and Young, Douglas and Fisher, Julie and Hauck, Marlene and Deiters, Alexander}, year={2010}, month={Aug}, pages={526} }
 @article{deiters_garner_lusic_govan_dush_nascone-yoder_yoder_2010, title={Photocaged Morpholino Oligomers for the Light-Regulation of Gene Function in Zebrafish and Xenopus Embryos}, volume={132}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja1053863}, DOI={10.1021/ja1053863}, abstractNote={Morpholino oligonucleotides, or morpholinos, have emerged as powerful antisense reagents for evaluating gene function in both in vitro and in vivo contexts. However, the constitutive activity of these reagents limits their utility for applications that require spatiotemporal control, such as tissue-specific gene disruptions in embryos. Here we report a novel and efficient synthetic route for incorporating photocaged monomeric building blocks directly into morpholino oligomers and demonstrate the utility of these caged morpholinos in the light-activated control of gene function in both cell culture and living embryos. We demonstrate that a caged morpholino that targets enhanced green fluorescent protein (EGFP) disrupts EGFP production only after exposure to UV light in both transfected cells and living zebrafish (Danio rerio) and Xenopus frog embryos. Finally, we show that a caged morpholino targeting chordin, a zebrafish gene that yields a distinct phenotype when functionally disrupted by conventional morpholinos, elicits a chordin phenotype in a UV-dependent manner. Our results suggest that photocaged morpholinos are readily synthesized and highly efficacious tools for light-activated spatiotemporal control of gene expression in multiple contexts.}, number={44}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Deiters, Alexander and Garner, R. Aaron and Lusic, Hrvoje and Govan, Jeane M. and Dush, Mike and Nascone-Yoder, Nanette M. and Yoder, Jeffrey A.}, year={2010}, month={Nov}, pages={15644–15650} }
 @article{morckel_young_deiters_nascone-yoder_2009, title={Light activated modulation of protein activity (Lamp): A tool for spatiotemporal control of signaling components in living embryos}, volume={331}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2009.05.359}, DOI={10.1016/j.ydbio.2009.05.359}, number={2}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Morckel, Allison and Young, Doug and Deiters, Alex and Nascone-Yoder, Nanette}, year={2009}, month={Jul}, pages={482} }
 @article{reed_womble_dush_tull_bloom_morckel_devlin_nascone-yoder_2009, title={Morphogenesis of the Primitive Gut Tube Is Generated by Rho/ROCK/Myosin II-Mediated Endoderm Rearrangements}, volume={238}, ISSN={["1097-0177"]}, DOI={10.1002/dvdy.22157}, abstractNote={During digestive organogenesis, the primitive gut tube (PGT) undergoes dramatic elongation and forms a lumen lined by a single-layer of epithelium. In Xenopus, endoderm cells in the core of the PGT rearrange during gut elongation, but the morphogenetic mechanisms controlling their reorganization are undetermined. Here, we define the dynamic changes in endoderm cell shape, polarity, and tissue architecture that underlie Xenopus gut morphogenesis. Gut endoderm cells intercalate radially, between their anterior and posterior neighbors, transforming the nearly solid endoderm core into a single layer of epithelium while concomitantly eliciting “radially convergent” extension within the gut walls. Inhibition of Rho/ROCK/Myosin II activity prevents endoderm rearrangements and consequently perturbs both gut elongation and digestive epithelial morphogenesis. Our results suggest that the cellular and molecular events driving tissue elongation in the PGT are mechanistically analogous to those that function during gastrulation, but occur within a novel cylindrical geometry to generate an epithelial-lined tube. Developmental Dynamics 238:3111–3125, 2009. © 2009 Wiley-Liss, Inc.}, number={12}, journal={DEVELOPMENTAL DYNAMICS}, author={Reed, Rachel A. and Womble, Mandy A. and Dush, Michel K. and Tull, Rhesa R. and Bloom, Stephanie K. and Morckel, Allison R. and Devlin, Edward W. and Nascone-Yoder, Nanette M.}, year={2009}, month={Dec}, pages={3111–3125} }
 @article{bloom_infante_everly_hanken_nascone-yoder_2009, title={Small molecule-mediated “phenotypic engineering” reveals a role for retinoic acid in anuran gut evolution}, volume={331}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2009.05.057}, DOI={10.1016/j.ydbio.2009.05.057}, number={2}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Bloom, Stephanie and Infante, Carlos and Everly, Anne and Hanken, James and Nascone-Yoder, Nanette}, year={2009}, month={Jul}, pages={400} }
 @article{nascone-yoder_dush_2009, title={Wnt/planar cell polarity signaling controls endoderm cell rearrangements during the morphogenesis of the primitive gut tube}, volume={331}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2009.05.237}, DOI={10.1016/j.ydbio.2009.05.237}, number={2}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Nascone-Yoder, Nanette and Dush, Michael}, year={2009}, month={Jul}, pages={450} }
 @article{ledon-rettig_pfennig_nascone-yoder_2008, title={Ancestral variation and the potential for genetic accommodation in larval amphibians: implications for the evolution of novel feeding strategies}, volume={10}, ISSN={["1525-142X"]}, DOI={10.1111/j.1525-142X.2008.00240.x}, abstractNote={SUMMARY Few studies provide empirical evidence for phenotypic plasticity's role in the evolution of novel traits. One way to do so is to test whether latent plasticity is present in an ancestor that can be refined, enhanced, or diminished by selection in derived taxa (through “genetic accommodation”), thereby producing novel traits. Here, we evaluated whether gut plasticity preceded and promoted the evolution of a novel feeding strategy in spadefoot toad tadpoles. We studied Scaphiopus couchii, whose tadpoles develop an elongate gut and consume only detritus, and two derived species, Spea multiplicata and Sp. bombifrons, whose tadpoles also express a novel, short-gut phenotype in response to a novel resource (anostracan shrimp). Consistent with the expectations of plasticity-mediated trait evolution, we found that shrimp induced a range of phenotypes in Scaphiopus that were not produced with detritus. This plasticity was either suppressed or exaggerated in Spea depending on whether the induced phenotypes were adaptive. Moreover, in contrast to its effects on morphology, shrimp induced little or no functional plasticity, as assessed by gut cell proliferation, in Scaphiopus. Shrimp did, however, induce substantial proliferation in Sp. bombifrons, the species that consumes the most shrimp and that produces the short-gut phenotype the most frequently. Thus, if Spea had ancestral morphological plasticity in response to a novel diet, their shrimp-induced short-gut morphology may have undergone subsequent genetic accommodation that improved its functionality. Hence, diet-induced phenotypic plasticity may have preceded and even promoted the evolution of a novel phenotype.}, number={3}, journal={EVOLUTION & DEVELOPMENT}, author={Ledon-Rettig, Cris C. and Pfennig, David W. and Nascone-Yoder, Nanette}, year={2008}, pages={316–325} }
 @article{nascone-yoder_reed_womble_dush_bloom_tull_morckel_2008, title={Basolumenal endoderm intercalation: A geometrically unique execution of convergent extension during gut tube elongation}, volume={319}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2008.05.167}, DOI={10.1016/j.ydbio.2008.05.167}, number={2}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Nascone-Yoder, Nanette and Reed, Rachel and Womble, Mandy and Dush, Michael and Bloom, Stephanie and Tull, Read and Morckel, Allison}, year={2008}, month={Jul}, pages={513} }
 @article{parr_young_dush_dieters_nascone-yoder_2008, title={Heterotaxin: A novel pyridine compound that perturbs left–right asymmetric organ morphogenesis}, volume={319}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2008.05.166}, DOI={10.1016/j.ydbio.2008.05.166}, number={2}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Parr, Meredith and Young, Doug and Dush, Michael and Dieters, Alex and Nascone-Yoder, Nanette}, year={2008}, month={Jul}, pages={513} }
 @article{bloom_infante_everly_hanken_nascone-yoder_2008, title={Small molecule-mediated “phenotypic engineering” reveals a role for retinoic acid in anuran gut evolution}, volume={319}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2008.05.109}, DOI={10.1016/j.ydbio.2008.05.109}, number={2}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Bloom, Stephanie and Infante, Carlos and Everly, Anne and Hanken, James and Nascone-Yoder, Nanette}, year={2008}, month={Jul}, pages={497–498} }
 @article{nascone-yoder_reed_2007, title={Rho GTPase signaling directs the late stage morphogenesis of the Xenopus digestive system}, volume={306}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2007.03.493}, DOI={10.1016/j.ydbio.2007.03.493}, number={1}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Nascone-Yoder, Nanette M. and Reed, Rachel A.}, year={2007}, month={Jun}, pages={441} }
 @article{lipscomb_schmitt_sablyak_yoder_nascone-yoder_2006, title={Role for retinoid signaling in left–right asymmetric digestive organ morphogenesis}, volume={235}, ISSN={1058-8388 1097-0177}, url={http://dx.doi.org/10.1002/dvdy.20879}, DOI={10.1002/dvdy.20879}, abstractNote={The looping events that establish left-right asymmetries in the vertebrate gut tube are poorly understood. Retinoic acid signaling is known to impact left-right development in multiple embryonic contexts, although its role in asymmetric digestive organ morphogenesis is unknown. Here, we show that the genes for retinaldehyde dehydrogenase (RALDH2) and a retinoic acid hydroxylase (CYP26A1) are expressed in complementary patterns in the Xenopus gut during looping. A late-stage chemical genetic assessment reveals that agonists and antagonists of retinoid signaling generate abnormal gut looping topologies, digestive organ heterotaxias, and intestinal malrotations. Accessory organ deformities commonly associated with intestinal malrotation in humans, such as annular pancreas, pancreas divisum, and extrahepatic biliary tree malformations, are also induced by distinct retinoid receptor agonists. Thus, late-stage retinoic acid signaling is likely to play a critical role in asymmetric gut tube morphogenesis and may underlie the etiology of several clinically relevant defects in the digestive system.}, number={8}, journal={Developmental Dynamics}, publisher={Wiley}, author={Lipscomb, Kristen and Schmitt, Christopher and Sablyak, Amanda and Yoder, Jeffrey A. and Nascone-Yoder, Nanette}, year={2006}, pages={2266–2275} }
 @article{gormley_nascone-yoder_2003, title={Left and right contributions to the Xenopus heart: implications for asymmetric morphogenesis}, volume={213}, ISSN={0949-944X 1432-041X}, url={http://dx.doi.org/10.1007/s00427-003-0337-5}, DOI={10.1007/s00427-003-0337-5}, number={8}, journal={Development Genes and Evolution}, publisher={Springer Science and Business Media LLC}, author={Gormley, Joseph P. and Nascone-Yoder, Nanette M.}, year={2003}, month={Aug}, pages={390–398} }
 @article{muller_prather_nascone-yoder_2003, title={Left-right asymmetric morphogenesis in theXenopus digestive system}, volume={228}, ISSN={1058-8388 1097-0177}, url={http://dx.doi.org/10.1002/dvdy.10415}, DOI={10.1002/dvdy.10415}, abstractNote={The morphogenetic mechanisms by which developing organs become left-right asymmetric entities are unknown. To investigate this issue, we compared the roles of the left and right sides of the Xenopus embryo during the development of anatomic asymmetries in the digestive system. Although both sides contribute equivalently to each of the individual digestive organs, during the initial looping of the primitive gut tube, the left side assumes concave topologies where the right side becomes convex. Of interest, the concave surfaces of the gut tube correlate with expression of the LR gene, Pitx2, and ectopic Pitx2 mRNA induces ectopic concavities in a localized manner. A morphometric comparison of the prospective concave and convex surfaces of the gut tube reveals striking disparities in their rate of elongation but no significant differences in cell proliferation. These results provide insight into the nature of symmetry-breaking morphogenetic events during left-right asymmetric organ development.}, number={4}, journal={Developmental Dynamics}, publisher={Wiley}, author={Muller, Jennifer K. and Prather, Deva R. and Nascone-Yoder, Nanette M.}, year={2003}, month={Nov}, pages={672–682} }
 @article{smith_grasty_theodosiou_tabin_nascone-yoder_2000, title={Evolutionary relationships between the amphibian, avian, and mammalian stomachs}, volume={2}, ISSN={1520-541X 1525-142X}, url={http://dx.doi.org/10.1046/j.1525-142x.2000.00076.x}, DOI={10.1046/j.1525-142x.2000.00076.x}, abstractNote={Although the gut is homologous among different vertebrates, morphological differences exist between different species. The most obvious variation in the guts of extant vertebrates appears in the stomach. To investigate the evolution of this structure, we compared the histology of the stomach and gastrointestinal tract in amphibian (Xenopus laevis), avian (Gallus gallus), and mammalian (Mus musculus) organisms, and defined the expression patterns of several genes within the developing guts of these lineages. In all three groups, we find that the anterior portion of the stomach has a similar glandular histology as well as a common embryonic expression of the secreted factors Wnt5a and BMP-4. Likewise, within the amniote lineages, the posterior nonglandular stomach and pyloric sphincter regions are also comparable in both histological and molecular phenotypes. The posterior stomach expresses Six2, BMPR1B, and Barx1, whereas the pyloric sphincter expresses Nkx2.5. Although the adult Xenopus stomach exhibits both glandular and aglandular regions and a distinct pyloric sphincter similar to that of the amniotic vertebrates, the histology of the Xenopus tadpole gut shows less distinct variation in differentiation in this region, which is most likely a derived condition. The molecular signature of the embryonic Xenopus gut correlates with the more derived morphology of the larval phase. We conclude that the global patterning of the gut is remarkably similar among the different vertebrate lineages. The distinct compartments of gene expression that we find in the gut be necessary for the unique morphological specializations that distinguish the stomachs from terrestrial vertebrates.}, number={6}, journal={Evolution and Development}, publisher={Wiley}, author={Smith, Devyn M. and Grasty, Rayetta C. and Theodosiou, Nicole A. and Tabin, Clifford J. and Nascone-Yoder, Nanette M.}, year={2000}, month={Nov}, pages={348–359} }
 @article{nascone_mercola_1997, title={Organizer Induction Determines Left–Right Asymmetry inXenopus}, volume={189}, ISSN={0012-1606}, url={http://dx.doi.org/10.1006/dbio.1997.8635}, DOI={10.1006/dbio.1997.8635}, abstractNote={Vertebrates appear bilaterally symmetrical but have considerable left-right (LR) asymmetry in the anatomy and placement of internal organs such as the heart. Although a number of asymmetrically expressed genes are known to affect LR patterning, both the initial source of asymmetry and the mechanism that correctly orients the LR axis remain controversial. In this study, we show that the induction of dorsal organizing centers in the embryo can orient LR asymmetry. Ectopic organizing centers were induced by microinjection of mRNA encoding a variety of body axis duplicating proteins, including members of the Wnt signal transduction pathway. The ectopic and primary body axes form side-by-side conjoined twins, with the secondary axis developing as either the left or right sibling. In all cases, correct LR asymmetry was observed in the left twin, regardless of whether it was derived from the primary axis or induced de novo by injection of Xwnt-8, beta-catenin, or Siamois mRNA. In contrast, the right twin was generally unbiased, regardless of the origin of the left body axis, as seen in many instances of experimentally induced and spontaneous conjoined twins. An unanticipated exception was that right twins induced by beta-catenin and Siamois, two downstream effectors of Wnt signaling, exhibited predominately normal heart looping, even when they formed the right twin. Taken together, these results indicate that LR asymmetry is locally oriented as a consequence of Wnt signaling through beta-catenin and Siamois. We discuss the possibility that signals upstream of beta-catenin and Siamois might be required in order for a right sibling to be randomized.}, number={1}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Nascone, Nanette and Mercola, Mark}, year={1997}, month={Sep}, pages={68–78} }
 @article{levin_nascone_1997, title={Two molecular models of initial left-right asymmetry generation}, volume={49}, ISSN={0306-9877}, url={http://dx.doi.org/10.1016/s0306-9877(97)90092-x}, DOI={10.1016/s0306-9877(97)90092-x}, abstractNote={Left-right (LR) asymmetry is a fascinating problem in embryonic morphogenesis. Recently, a pathway of genes has been identified which is involved in LR patterning in vertebrates. Although this work characterizes the interactions of several asymmetrically-expressed genes, it is still entirely unclear how such asymmetric expression is set up in the first place. There are two promising molecular candidates which may play a role is such a process: the motor protein dynein, and the gap junction protein connexin-43 (Cx43). We present two models, significantly supported by previous findings, which hypothesize that (a) dynein asymmetrically localizes LR determinants in individual cells to establish cell-autonomous LR biasing, and (b) asymmetric activity of Cx43 gap junctions within key cells sets up electric potentials in multicellular fields, thus establishing large-scale LR asymmetry.}, number={5}, journal={Medical Hypotheses}, publisher={Elsevier BV}, author={Levin, M. and Nascone, N.}, year={1997}, month={Nov}, pages={429–435} }
 @article{nascone_mercola_1996, title={Endoderm and Cardiogenesis}, volume={6}, ISSN={1050-1738}, url={http://dx.doi.org/10.1016/s1050-1738(96)00086-2}, DOI={10.1016/s1050-1738(96)00086-2}, abstractNote={Classic studies of vertebrate heart development have implicated the endoderm in an inductive role, based on its ability to induce rhythmic beating in explants of presumptive heart mesoderm. Recent experiments, aided by the use of heart-specific molecular markers, have defined discrete phases of cardiogenesis that depend on endodermal signals for functional contractility. In addition, the ability of the endoderm to generate a beating heart from tissues fated to form other cell types suggests that endoderm may also be involved in the initial specification of the early heart field.}, number={7}, journal={Trends in Cardiovascular Medicine}, publisher={Elsevier BV}, author={Nascone, Nanette and Mercola, Mark}, year={1996}, month={Oct}, pages={211–216} }
 @article{nascone_mercola_1995, title={An inductive role for the endoderm in Xenopus cardiogenesis}, volume={121}, journal={Development}, author={Nascone, N. and Mercola, M.}, year={1995}, pages={515–523} }