In the present study using zebrafish as the model organism, we have investigated the function of UII/UII-receptor (UIIR) signaling pathway during early embryogenesis. Herein we presented five lines of evidence supporting the hypothesis that UII/ UIIR signaling pathway is required for normal determination of asymmetric axis during early embryogenesis. First, function-loss of UII results in a concordant randomization of viscus asymmetries in embryos, including abnormalities in cardiac looping and positioning of visceral organs. Second, knockdown of UII randomizes the left-sided expression of asymmetrical genes including lefty2, spaw and pitx2c in the lateral plate mesoderm (LPM) and bmp4 in the developing heart domain and the LPM. Third, reduced UII levels interfere with the normal organogenesis of Kupffer's vesicle (KV), an organ implicated in the early steps of left-right (L-R) patterning of embryos. Fourth, repression of UII function perturbs the asymmetrical distribution of free Ca2+ (intracellular Ca2+) at the region surrounding embryo KV during early somitogenesis, which is one of the signaling mechanisms that propagandize and amplify the early clue of left-right (L-R) asymmetry. Fifth, depressing UII levels alters the normal pattern of Bmp and Nodal signaling, which modulate the establishment of L-R axis of developmental embryo. Collectively, these observations support a model in which UII/UIIR signal system takes part in the early molecular events of L-R asymmetry patterning of embryo by modulating Bmp and Nodal signaling, regulating KV normal morphogenesis, so then, maintaining the asymmetrical distribution of free intracellular Ca2+ at the peripheral region surrounding embryo KV. This study documents a role of UII/UIIR signaling pathway in the establishment of L-R axis of embryos which promises to reveal the molecular mechanisms responsible for human congenital diseases with heterotaxy. / Urotensin II (UII) is the most potent vasoconstrictor identified so far. This cyclic peptide stimulates its G protein-coupled receptor (GPR) to modulate cardiovascular system function in humans and in other animal species. / Li, Jun. / Advisers: Christopher HK Cheng; Mingliang He. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 143-168). / 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_344693 |
| Date | January 2010 |
| Contributors | Li, Jun, Chinese University of Hong Kong Graduate School. Division of Public Health. |
| 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 (xvi, 172 leaves : ill.) |
| 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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