Date on Master's Thesis/Doctoral Dissertation

5-2020

Document Type

Master's Thesis

Degree Name

M.S.

Department

Oral Biology

Degree Program

Oral Biology, MS

Committee Chair

Sandell, Lisa

Committee Member

Ding, Jixiang

Committee Member

Durski, Marcelo

Author's Keywords

RDH10; lung branching; retinoic acid; vitamin A defficiency

Abstract

Birth defects are complicated pathological processes. Many birth defects can be traced back to disrupted regulation of molecular signaling pathways during embryogenesis. One of the most important gene regulatory factors during embryo development is retinoic acid (RA). However, studying the specific roles of RA in each organ during embryogenesis in vivo is challenging. The Sandell laboratory has a conditional mutant mouse model that can potentially be used for studying the role of RA during embryogenesis by inducing stage-specific RA deficiency. This model allows retinol dehydrogenase 10 (Rdh10), a gene required for RA production, to be inactivated at a chosen time by exposing the embryos to the drug tamoxifen. However, in order for this conditional genetic inactivation model to be used for rigorous analysis of birth defects resulting from RA deficiency, it is essential to know the kinetics of Rdh10 gene inactivation following exposure to the inducing drug tamoxifen. In order to characterize the conditional Rdh10 mutant model so that it can be useful to study the impact of RA deficiency on birth defects, I have determined the kinetics of the inactivation Rdh10 upon exposure of the embryos to tamoxifen. My characterization of the conditional Rdh10 inactivation kinetics was useful to other researchers, enabling them to use stage-specific Rdh10 inactivation to identify new roles for RA in embryonic development, such as in formation of salivary glands and secondary palate. The characterization of the 6conditional Rdh10 inactivation kinetics was also useful for my analysis of RA role in lung branching morphogenesis later. Using the stage-specific Rdh10 inactivation model I identified that RA is important for lung branching after the formation of the lung buds. Gene expression analysis revealed that the defects in lung branching morphogenesis of Rdh10 mutant embryos were not associated with mis-regulation of the known RA-regulated gene Fgf10, but were associated with overexpression of Ctgf and Mgp.

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