Author ORCID Identifier


Date of Graduation


Document Type

Thesis (MS)

Program Affiliation

Biomedical Sciences

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Jun Wang, PhD

Committee Member

Richard Behringer, PhD

Committee Member

Peter Lwigale, PhD

Committee Member

James Martin, MD, PhD

Committee Member

Rachel Miller, PhD


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.


neural crest cells, congenital heart defects, heart development, embryogenesis, Hippo signaling pathway, Yap and Taz



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.