Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development

Bibliographic Details
Main Author: Dohn, Tracy E.
Language:English
Published: University of Cincinnati / OhioLINK 2015
Subjects:
Wnt
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427983237
id ndltd-OhioLink-oai-etd.ohiolink.edu-ucin1427983237
record_format oai_dc
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin14279832372021-08-03T06:29:47Z Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development Dohn, Tracy E. Developmental Biology heart development signaling Wnt Nr2f1a 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. 2015-06-02 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427983237 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427983237 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Developmental Biology
heart
development
signaling
Wnt
Nr2f1a
spellingShingle Developmental Biology
heart
development
signaling
Wnt
Nr2f1a
Dohn, Tracy E.
Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development
author Dohn, Tracy E.
author_facet Dohn, Tracy E.
author_sort Dohn, Tracy E.
title Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development
title_short Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development
title_full Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development
title_fullStr Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development
title_full_unstemmed Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development
title_sort roles of wnt signaling and nr2f1a during zebrafish cardiac development
publisher University of Cincinnati / OhioLINK
publishDate 2015
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427983237
work_keys_str_mv AT dohntracye rolesofwntsignalingandnr2f1aduringzebrafishcardiacdevelopment
_version_ 1719437947924643840