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The role of endogenous retinoic acid in jaw development

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Title: The role of endogenous retinoic acid in jaw development
Author: Fan, Churmy Yong
Degree Master of Science - MSc
Program Cell and Developmental Biology
Copyright Date: 2011
Publicly Available in cIRcle 2011-09-19
Abstract: The aim of this thesis is to study the effects of reducing retinoic acid (RA) levels in the embryonic face on jaw morphogenesis. One member of the Cytochrome P26 class of enzymes, CYP26A1, which degrades retinol products, was locally overexpressed in chicken embryos. I hypothesized that lowering RA levels would either affect jaw patterning, cell survival and/or cytodifferentiation. Chicken embryos at stage 15 and 20 (E2.5, 3.5) were injected with RCAS::hCYP26A1 in one of three facial prominences, frontonasal mass, maxillary and mandibular prominence. Embryos were fixed 12 days later at stage 39 to examine external and skeletal anatomy. Virus injection into stage 15 and 20 embryos showed similar phenotypes except that embryos injected at stage 15 were more severely affected. Almost all embryos injected at stage 15 had reduced cartilage and bone and some injected in the frontonasal mass and maxillary prominence showed clefts. I next investigated whether endogenous RA levels were reduced by the virus. Wholemount in situ hybridization showed that RARβ, a direct target of RA signaling, and RALDH2, a RA synthesizing enzyme, were downregulated on the treated side. Expression of indirect targets of RA were also tested but were generally unaffected. The use of a RARE-luciferase reporter showed that the response to exogenous RA was inhibited when CYP26A1 virus was present, though not by a significant amount. Thus the RARβ gene expression and luciferase data suggest the CYP26A1 virus had moderately decreased the levels of RA. The mechanism underlying bone and cartilage differentiation phenotype was examined next. I found that phenotypes could be detected as early as stage 30. There was decreased area of alkaline phosphatase staining and decreased cross sectional area of Meckel’s cartilage in treated embryos. Cell proliferation was decreased and apoptosis was increased in the bone condensations, however cellular dynamics were unaffected in Meckel’s cartilage. In conclusion, RA is required for expansion of intramembranous bone and cartilage condensations in a stage but not position specific manner.
URI: http://hdl.handle.net/2429/37477
Scholarly Level: Graduate

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