Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development
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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. |
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NDLTD |
language |
English |
sources |
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topic |
Developmental Biology heart development signaling Wnt Nr2f1a |
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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 |
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1719437947924643840 |