Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


13924.pdf (26.82 MB)

ETD Abstract Container

Abstract Header

Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development

Dohn, Tracy E.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427983237

Abstract Details

2015, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
Congenital heart defects are found in over 1% of live births. The cardiovascular system is required throughout development and adulthood to efficiently transport oxygen, nutrients, and waste products through the body. The size and structure of the heart muscle plays a key role in the efficiency of the heart to pump blood throughout the body. This dissertation focuses on developmental signaling events that set up the initial cardiac cell population and subsequent organ size. We investigate the temporal requirements for the Wnt signaling pathway in cardiac development, and the role of Nr2f proteins downstream of retinoic acid signaling in cardio-pharyngeal cell specification. Previous studies indicate that heart development requires reiterative phases of canonical Wnt/ß-catenin (Wnt) signaling. Here, we find three early phases of Wnt signaling regulate cardiac cell numbers. Wnt signaling promotes mesoderm and pre-cardiac mesoderm specification, is sufficient to inhibit cardiomyocyte differentiation, and promotes the differentiation of additional atrial cells. Interestingly, the inhibition of cardiomyocyte differentiation by Wnt signaling leads to cardiac progenitor cell death through a p53/Caspase-3 independent mechanism. Together with a report for a late role for Wnt signaling in restricting ventricular cell proliferation, our results indicate four distinct phases of Wnt signaling during the first three days of zebrafish development. We also examined downstream effectors of RA signaling, specifically Nr2f1a in zebrafish, as a regulator of early cardiac progenitor specification. Our results indicate that Nr2f proteins might have an early role in specification of the cardiac progenitor field in addition to the previously described later role in atrial cell specification. Interestingly, Nr2f1a regulates the cardiac field through mediating a cardio-pharyngeal fate decision, promoting pharyngeal muscle development at the expense of cardiac progenitor specification. These results demonstrate the complexity of cardiac progenitor cell regulation during early development and give new insight into the temporal requirements of Wnt signaling and regulation of the vertebrate cardio-pharyngeal progenitor pool.
Joshua Waxman, Ph.D. (Committee Chair)
Brian Gebelein, Ph.D. (Committee Member)
Jerry Lingrel, Ph.D. (Committee Member)
Saulius Sumanas, Ph.D. (Committee Member)
Katherine Yutzey, Ph.D. (Committee Member)
142 p.
Developmental Biology
heart; development; signaling; Wnt; Nr2f1a

Recommended Citations

Citations

  • Dohn, T. E. (2015). Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427983237

    APA Style (7th edition)

  • Dohn, Tracy. Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development. 2015. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427983237.

    MLA Style (8th edition)

  • Dohn, Tracy. "Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development." Doctoral dissertation, University of Cincinnati, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427983237

    Chicago Manual of Style (17th edition)

ucin1427983237
288
© 2015, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.