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Roles of Retinoic Acid and Wnt Signaling during Zebrafish Development

Mandal, Amrita
http://orcid.org/0000-0002-7459-4919
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1459528244

Abstract Details

2016, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
Retinoic acid (RA) and canonical Wnt/ß-catenin (Wnt) signaling are two major pathways that direct early embryonic development. Abnormalities in either pathway lead to congenital birth defects of the limb, heart and central nervous systems. This thesis is comprised of three studies that provide novel insights into the roles of RA and Wnt signaling during zebrafish development. Utilizing a ligand trap method, we created new zebrafish transgenic RA reporters, which act as a direct sensor for RA. We have shown these novel transgenic lines are responsive to RA and report previously unknown areas of activity. These reporters will be valuable tools to aid in studying early embryonic RA signaling and responses. Crossregulation of RA and Wnt signaling has been reported in different cell types and physiological conditions with clinical and physiological relevance. Both RA and Wnt regulate Dact (Dapper antagonist of catenin) proteins, thus this family of proteins might act as a linker between these two pathways in various developmental processes. With that aim we have examined the dynamic expression pattern and regulation of dact3 genes in zebrafish. Our analysis has shown dact3b but not dact3a is negatively regulated by RA in the hindbrain. Multiple congenital defects include both cardiac and craniofacial abnormalities, which suggest there is close relationship between adjacent cardiac and pharyngeal field. Signaling pathways that regulate progenitor specification in the cardiopharyngeal field (CPF) are not yet well understood. Previous studies have shown that Wnt promotes cardiac specification and inhibits pharyngeal muscle (PM) development during somitogenesis. Our work demonstrates that contrary to previous studies, Wnt signaling promotes PM loss only prior to gastrulation, and interestingly this timing correlates with increases in cardiac specification. We also find that excess Wnt leads to an increase of differentiated first heart field (FHF) and a decrease in second heart field (SHF) and PM markers. Altogether, these results provide a novel tool to study RA signaling as well as opens up new areas to stud RA and Wnt cross regulaion of the context of dact3b. Additionally, we have provided new insights on the role of Wnt during fate specification in the CPF.
Joshua Waxman, Ph.D. (Committee Chair)
Louis Muglia, M.D. Ph.D. M (Committee Member)
Brian Gebelein, Ph.D. (Committee Member)
Jerry Lingrel, Ph.D. (Committee Member)
Katherine Yutzey, Ph.D. (Committee Member)
147 p.
Biology
Zebrafish; Retinoic acid; Wnt Signaling; Cardiac; Pharyngeal; Development

Recommended Citations

Citations

  • Mandal, A. (2016). Roles of Retinoic Acid and Wnt Signaling during Zebrafish Development [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1459528244

    APA Style (7th edition)

  • Mandal, Amrita. Roles of Retinoic Acid and Wnt Signaling during Zebrafish Development. 2016. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1459528244.

    MLA Style (8th edition)

  • Mandal, Amrita. "Roles of Retinoic Acid and Wnt Signaling during Zebrafish Development." Doctoral dissertation, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1459528244

    Chicago Manual of Style (17th edition)

ucin1459528244
251
© 2016, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.