Congenital heart defects (CHDs) are the most common human birth defect, occurring in ~1/100 newborns, and are a leading cause of early infant death. Cardiac neural crest cells (NCCs) are a migratory and multipotent cell population known to aid in the development of the cardiac outflow tract (OFT), valves, and interventricular septum, during embryogenesis. Yap and Taz are downstream effectors of the fundamental Hippo signaling pathway and are vital for proper organ and tissue development, yet their role in neural crest (NC)-derived heart formation is still largely unknown. We generated Yap and Taz conditional knockout (CKO) mice using a Cre-lox system, by the use of Yap and Taz CKO alleles and the NC-specific Cre drivers Wnt1-Cre and Wnt1-Cre2SOR, which leads to abnormal cardiac formation, mimicking human CHD phenotypes. Yap+/-; Taz-/- CKO mutants produced various OFT and remodeling defects including ventricular septal defect (VSD), tetralogy of Fallot (TOF), double outlet right ventricle (DORV), and cardiac valve aberrations, varyingly between embryonic day (E) 14.5, E16.5, and E18.5. Cell apoptosis, proliferation, and smooth muscle differentiation were unchanged in Yap+/-; Taz-/- CKO mutants. Comparably, Yap+/-; Taz+/- double heterozygous hearts exhibited external morphology similar to that of controls, but sectioning revealed mild VSD, along with cardiac valve leaflet irregularities, at E16.5 and E18.5. Compelling preliminary RNA-sequencing data together with transwell migration assay, scratch assay, and ex vivo culture, indicate a potential role for Yap/Taz in regulating NC migration. Together, our data indicate that Yap/Taz play a critical role in proper cardiac NC-derived cardiac formation.
","abstract_html":"<p>Congenital heart defects (CHDs) are the most common human birth defect, occurring in ~1/100 newborns, and are a leading cause of early infant death. Cardiac neural crest cells (NCCs) are a migratory and multipotent cell population known to aid in the development of the cardiac outflow tract (OFT), valves, and interventricular septum, during embryogenesis. <em>Yap </em>and <em>Taz </em>are downstream effectors of the fundamental Hippo signaling pathway and are vital for proper organ and tissue development, yet their role in neural crest (NC)-derived heart formation is still largely unknown. We generated <em>Yap </em>and <em>Taz </em>conditional knockout (CKO) mice using a Cre-lox system, by the use of <em>Yap </em>and <em>Taz </em>CKO alleles and the NC-specific Cre drivers <em>Wnt1-Cre </em>and <em>Wnt1-Cre2SOR, </em>which leads to abnormal cardiac formation, mimicking human CHD phenotypes. <em>Yap<sup>+/-</sup>; Taz<sup>-/-</sup> </em>CKO mutants produced various OFT and remodeling defects including ventricular septal defect (VSD), tetralogy of Fallot (TOF), double outlet right ventricle (DORV), and cardiac valve aberrations, varyingly between embryonic day (E) 14.5, E16.5, and E18.5. Cell apoptosis, proliferation, and smooth muscle differentiation were unchanged in <em>Yap<sup>+/-</sup>; Taz<sup>-/-</sup> </em>CKO mutants. Comparably, <em>Yap<sup>+/-</sup>; Taz<sup>+/-</sup> </em>double heterozygous hearts exhibited external morphology similar to that of controls, but sectioning revealed mild VSD, along with cardiac valve leaflet irregularities, at E16.5 and E18.5. Compelling preliminary RNA-sequencing data together with transwell migration assay, scratch assay, and <em>ex vivo </em>culture, indicate a potential role for <em>Yap/Taz</em> in regulating NC migration. Together, our data indicate that <em>Yap/Taz</em> play a critical role in proper cardiac NC-derived cardiac formation.</p>","abstract_has_math":false,"creators":["Erhardt, Shannon","0000-0002-0189-0012
"],"institution":null,"degree_name":"Masters of Science (MS)","degree_level":"Thesis (MS)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Jun Wang, PhD","Richard Behringer, PhD","Peter Lwigale, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-08-01T07:00:00Z","date_published":"2022-08-01T07:00:00Z","updated_at":"2026-07-24T05:49:54Z","subjects":["neural crest cells","congenital heart defects","heart development","embryogenesis","Hippo signaling pathway","Yap and Taz","Biology","Cell and Developmental Biology","Genetics and Genomics","Medical Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1217","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Jun Wang, PhD","Richard Behringer, PhD","Peter Lwigale, PhD"]},{"key":"dc:creator","label":"Author","values":["Erhardt, Shannon","0000-0002-0189-0012
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"]},{"key":"dc:title","label":"Title","values":["Yap and Taz Are Required For Neural Crest-Derived Cardiovascular Development"]}]}],"canonical_facts":{"dc:contributor":["Jun Wang, PhD","Richard Behringer, PhD","Peter Lwigale, PhD"],"dc:creator":["Erhardt, Shannon","0000-0002-0189-0012
"],"dc:date.available":["2023-08-05T07:00:00Z"],"dc:description.abstract":["Congenital heart defects (CHDs) are the most common human birth defect, occurring in ~1/100 newborns, and are a leading cause of early infant death. Cardiac neural crest cells (NCCs) are a migratory and multipotent cell population known to aid in the development of the cardiac outflow tract (OFT), valves, and interventricular septum, during embryogenesis. Yap and Taz are downstream effectors of the fundamental Hippo signaling pathway and are vital for proper organ and tissue development, yet their role in neural crest (NC)-derived heart formation is still largely unknown. We generated Yap and Taz conditional knockout (CKO) mice using a Cre-lox system, by the use of Yap and Taz CKO alleles and the NC-specific Cre drivers Wnt1-Cre and Wnt1-Cre2SOR, which leads to abnormal cardiac formation, mimicking human CHD phenotypes. Yap+/-; Taz-/- CKO mutants produced various OFT and remodeling defects including ventricular septal defect (VSD), tetralogy of Fallot (TOF), double outlet right ventricle (DORV), and cardiac valve aberrations, varyingly between embryonic day (E) 14.5, E16.5, and E18.5. Cell apoptosis, proliferation, and smooth muscle differentiation were unchanged in Yap+/-; Taz-/- CKO mutants. Comparably, Yap+/-; Taz+/- double heterozygous hearts exhibited external morphology similar to that of controls, but sectioning revealed mild VSD, along with cardiac valve leaflet irregularities, at E16.5 and E18.5. Compelling preliminary RNA-sequencing data together with transwell migration assay, scratch assay, and ex vivo culture, indicate a potential role for Yap/Taz in regulating NC migration. Together, our data indicate that Yap/Taz play a critical role in proper cardiac NC-derived cardiac formation.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1217"],"dc:subject":["neural crest cells","congenital heart defects","heart development","embryogenesis","Hippo signaling pathway","Yap and Taz","Biology","Cell and Developmental Biology","Genetics and Genomics","Medical Sciences"],"dc:title":["Yap and Taz Are Required For Neural Crest-Derived Cardiovascular Development"],"thesis:degree_level":["Thesis (MS)"],"thesis:degree_name":["Masters of Science (MS)"]},"updated_at":"2026-07-24T05:49:54Z"}