All-trans retinoic acid (atRA) is an important morphogen in many developmental processes, including apoptosis, growth, organogenesis and differentiation. During the early embryonic development, atRA is synthesized in an irreversible reaction from all-trans retinal (atRAL), catalyzed mainly by retinal dehydrogenase 2 (RALDH2). The upstream metabolic pathway, including the redox reaction between all-trans retinol (atROL) and atRAL, mediated by short-chain dehydrogenase/reductase, however, is less understood during embryonic development. / Previously a Xenopus laevis short-chain dehydrogenase/reductase 3 (dhrs3) was identified as a gene differentially expressed in the Spemann-Mangold Organizer. In this study, dhrs3 was found to be expressed in the circumblastoporal ring, neuroectoderm and pronephros region, and was up-regulated by atRA signalling. By using loss-of-function and gain-of-function approaches, it was found that the phenotype induced by knockdown of dhrs3 mimicked those with an elevated level of atRA signalling, and overexpression of dhrs3 enhanced the phenotype of cyp26a1, which functions in degradation of atRA. In dhrs3 knock-down embryos (morphants), expression domain of the mesoderm markers brachyury was disrupted, and that of organizer marker lim1 were significantly expanded, suggesting altered mesoderm induction. Overexpression of dhrs3, on the other hand, exerted an opposite effect on lim1 by reducing its expression. dhrs3 also rescued the phenotype following raldh2 overexpression induced by exogenous atRAL, suggesting that dhrs3 competed with raldh2 for the same substrate, atRAL. In line with these findings, expression of the mid-brain, hindbrain and neural crest markers was posteriorized in dhrs3-overexpressing embryos, similar to the phenotype of atRA-deficient embryos induced by cyp26a1. These findings indicate that dhrs3 participates in the retinoid metabolism by reducing atRAL to atROL. / Xenopus dhrs3 morphants displayed a shortened anteroposterior axis, similar to that of atRA toxicity. Examination of convergent extension (CE) markers papc indicated a defect in the CE movement, which was also evidenced by the disrupted bra and not expression. Overall, the results of the present study suggest that dhrs3 regulates proper mesoderm patterning through regulating the CE movement. / Kam, Kin Ting. / Advisers: Yu Pang Eric Cho; Wood Yee Chan; Hui Zhao. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves [158]-184). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344976 |
| Date | January 2011 |
| Contributors | Kam, Kin Ting., Chinese University of Hong Kong Graduate School. Division of Anatomy. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (184 leaves : ill. (some col.)) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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