@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={ABSTRACT
               The morphogenesis of left-right (LR) asymmetry is a crucial 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-minded 2 (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} }
 @article{pohl_medland_mackey_edwards_bagley_dewilde_williams_moeser_2017, title={Early weaning stress induces chronic functional diarrhea, intestinal barrier defects, and increased mast cell activity in a porcine model of early life adversity}, volume={29}, ISSN={["1365-2982"]}, DOI={10.1111/nmo.13118}, abstractNote={AbstractBackgroundEarly life adversity (ELA) is a risk factor for development of gastrointestinal disorders later in life. The underlying mechanisms through which ELA and sex interact to influence disease susceptibility remains poorly understood.MethodsUtilizing a porcine early weaning stress (EWS) model to mimic ELA, we investigated the long‐term effects of EWS on functional diarrhea, ileal permeability, mast cell activity and mast cell relationship with enteric ganglia.Key ResultsJuvenile and adult EWS pigs exhibited chronic, functional diarrhea (EWS 43.6% vs late wean control(LWC) 4.8%, P<.0001), increased intestinal permeability (2 fold increase EWS vs LWC, P<.0001), and mast cell numbers (at 7 weeks and 20 weeks ~1.6 fold increase EWS vs LWC, P<.05). Compared with EWS male castrates (Male‐C), females EWS pigs exhibited more frequent diarrhea (58.8% vs 29.9%, P=.0016), and increased intestinal permeability (1‐2 fold higher in EWS females, P<.001). Increased mast cell numbers and their enhanced co‐localization with neuronal ganglia were observed in both Male‐C and female EWS pigs; however, female pigs exhibited greater release of mast cell tryptase upon activation with c48/80 (~1.5 fold increase, P<.05), compared with Male‐C pigs.Conclusions and InferencesThese data demonstrate that pigs exposed to ELA exhibit increased vulnerability to functional diarrhea, intestinal permeability and mast cell activity. Further, these studies also showed that EWS female and Male‐C pigs exhibited dimorphic responses to EWS with female piglets exhibited greater susceptibility and severity of diarrhea, intestinal permeability and mast cell tryptase release. Together, these findings mimic some of the key pathophysiologic findings in human functional GI disorders functional gastrointestinal disorders (FGIDs) suggesting that the EWS porcine model could be a valuable preclinical translational model for FGID research associated with ELA.}, number={11}, journal={NEUROGASTROENTEROLOGY AND MOTILITY}, author={Pohl, C. S. and Medland, J. E. and Mackey, E. and Edwards, L. L. and Bagley, K. D. and DeWilde, M. P. and Williams, K. J. and Moeser, A. J.}, year={2017}, month={Nov} }
 @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} }