@article{grzymkowski_chiu_jima_wyatt_jayachandran_stutts_nascone-yoder_2024, title={Developmental regulation of cellular metabolism is required for intestinal elongation and rotation}, volume={151}, ISSN={["1477-9129"]}, url={https://doi.org/10.1242/dev.202020}, DOI={10.1242/dev.202020}, abstractNote={ABSTRACT}, number={1}, journal={DEVELOPMENT}, author={Grzymkowski, Julia K. and Chiu, Yu-Chun and Jima, Dereje D. and Wyatt, Brent H. and Jayachandran, Sudhish and Stutts, Whitney L. and Nascone-Yoder, Nanette M.}, year={2024}, month={Jan} } @article{davis_wiegers_wiegers_wyatt_johnson_sciaky_barkalow_strong_planchart_mattingly_2023, title={CTD tetramers: a new online tool that computationally links curated chemicals, genes, phenotypes, and diseases to inform molecular mechanisms for environmental health}, volume={195}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfad069}, abstractNote={Abstract}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Davis, Allan Peter and Wiegers, Thomas C. and Wiegers, Jolene and Wyatt, Brent and Johnson, Robin J. and Sciaky, Daniela and Barkalow, Fern and Strong, Melissa and Planchart, Antonio and Mattingly, Carolyn J.}, year={2023}, month={Sep}, pages={155–168} } @article{blue_white_dush_gordon_wyatt_white_marvin_helle_ojala_priest_et al._2023, title={Rare variants in CAPN2 increase risk for isolated hypoplastic left heart syndrome}, volume={4}, ISSN={["2666-2477"]}, DOI={10.1016/j.xhgg.2023.100232}, abstractNote={Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD) characterized by hypoplasia of the left ventricle and aorta along with stenosis or atresia of the aortic and mitral valves. HLHS represents only ∼4-8% of all CHDs but accounts for ∼25% of deaths. HLHS is an isolated defect (i.e., iHLHS) in 70% of families, the vast majority of which are simplex. Despite intense investigation, the genetic basis of iHLHS remains largely unknown. We performed exome sequencing on 331 families with iHLHS aggregated from four independent cohorts. A Mendelian model-based analysis demonstrated that iHLHS was not due to single, large effect alleles in genes previously reported to underlie iHLHS or CHD in >90% of families in this cohort. Gene-based association testing identified increased risk for iHLHS associated with CAPN2 (p=1.8x10-5), encoding a protein involved in functional adhesion. Functional validation studies in a vertebrate animal model (Xenopus laevis) confirmed CAPN2 is essential for cardiac ventricle morphogenesis, that in vivo loss of calpain function causes hypoplastic ventricle phenotypes, and suggest that human CAPN2707C>T and CAPN21112C>T variants, each found in multiple individuals with iHLHS, are hypomorphic alleles. Collectively, our findings show that iHLHS is typically not a Mendelian condition, demonstrate that CAPN2 variants increase risk of iHLHS, and identify a novel pathway involved in HLHS pathogenesis.}, number={4}, journal={HUMAN GENETICS AND GENOMICS ADVANCES}, author={Blue, Elizabeth E. and White, Janson J. and Dush, Michael K. and Gordon, William W. and Wyatt, Brent H. and White, Peter and Marvin, Colby T. and Helle, Emmi and Ojala, Tiina and Priest, James R. and et al.}, year={2023}, month={Oct} } @article{dickinson_turner_wahl_kennedy_wyatt_howton_2022, title={E-liquids and vanillin flavoring disrupts retinoic acid signaling and causes craniofacial defects in Xenopus embryos}, volume={481}, ISSN={["1095-564X"]}, DOI={10.1016/j.ydbio.2021.09.004}, abstractNote={Environmental teratogens such as smoking are known risk factors for developmental disorders such as cleft palate. While smoking rates have declined, a new type of smoking, called vaping is on the rise. Vaping is the use of e-cigarettes to vaporize and inhale an e-liquid containing nicotine and food-like flavors. There is the potential that, like smoking, vaping could also pose a danger to the developing human. Rather than waiting for epidemiological and mammalian studies, we have turned to an aquatic developmental model, Xenopus laevis, to more quickly assess whether e-liquids contain teratogens that could lead to craniofacial malformations. Xenopus, like zebrafish, has the benefit of being a well-established developmental model and has also been effective in predicting whether a chemical could be a teratogen. We have determined that embryonic exposure to dessert flavored e-liquids can cause craniofacial abnormalities, including an orofacial cleft in Xenopus. To better understand the underlying mechanisms contributing to these defects, transcriptomic analysis of the facial tissues of embryos exposed to a representative dessert flavored e-liquid vapor extract was performed. Analysis of differentially expressed genes in these embryos revealed several genes associated with retinoic acid metabolism or the signaling pathway. Consistently, retinoic acid receptor inhibition phenocopied the craniofacial defects as those embryos exposed to the vapor extract of the e-liquid. Such malformations also correlated with a group of common differentially expressed genes, two of which are associated with midface birth defects in humans. Further, e-liquid exposure sensitized embryos to forming craniofacial malformations when they already had depressed retinoic acid signaling. Moreover, 13-cis-retinoic acid treatment could significantly reduce the e-liquid induced malformation in the midface. Such results suggest the possibility of an interaction between retinoic acid signaling and e-liquid exposure. One of the most popular and concentrated flavoring chemicals in dessert flavored e-liquids is vanillin. Xenopus embryos exposed to this chemical closely resembled embryos exposed to dessert-like e-liquids and a retinoic acid receptor antagonist. In summary, we determined that e-liquid chemicals, in particular vanillin, can cause craniofacial defects potentially by dysregulating retinoic acid signaling. This work warrants the evaluation of vanillin and other such flavoring additives in e-liquids on mammalian development.}, journal={DEVELOPMENTAL BIOLOGY}, author={Dickinson, Amanda J. G. and Turner, Stephen D. and Wahl, Stacey and Kennedy, Allyson E. and Wyatt, Brent H. and Howton, Deborah A.}, year={2022}, month={Jan}, pages={14–29} } @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}, 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}, number={19}, journal={DEVELOPMENT}, author={Grzymkowski, Julia and Wyatt, Brent and Nascone-Yoder, Nanette}, year={2020}, month={Oct} }