碩士 / 國立臺灣大學 / 分子與細胞生物學研究所 / 96 / ADP-ribosylation-like factor-6 interacting protein (Arl6ip) is an interacting protein of Arl6 which is one of the small ADP ribosylation factor GTP-binding proteins that are major regulators in intracellular traffic. Fan et al. (2004) identified Arl6 as the gene underlying Bardet-Biedl syndrome type 3 (BBS3), a multisystemic disorder characterized by obesity, blindness, polydactyly, renal abnormalities and cognitive impairment. Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung’s disease in BBS (Tobin et al., 2008). It means that BBS associated genes must involve in neural crest development. Although the in vitro function of Arl6ip gene is suggested as protein transport, membrane trafficking, or cell signaling during hematopoietic maturation, the in vivo roles that alr6ip plays in BBS and neural crest development are totally unknown. Here, we demonstrated that when Arl6ip function was lost by injecting the zebrafish embryos an antisense morpholino oligonucleotides (MO) which inhibited Arl6ip mRNA translation specifically, the neural crest derivatives, such as cartilage, cranial ganglia, peripheral neurons, and heart, were defective. These defects are similar to Bardet-Biedl syndrome. The expressions of neural plate border specifiers, msxb, dlx3b, and pax3 were normal, but the expression of neural crest specification genes, foxd3, snail1b, and sox10 were reduced, implicating Arl6ip is essential for neural crest specification, but not for neural crest induction. Furthermore, crestin and sox10, which were expressed in the cranial and trunk migrating neural crest cells, were also decreased, suggesting that Arl6ip is required for neural crest migration. In addition, apoptosis was apparent occurrence in the pre-migratory neural crest cells, indicating a critical role for arl6ip in the survival of neural crest cells. Interestingly, we noticed that the hearts of the Arl6ip-MO-injected embryos were failure to undergo normal looping and the function of heart was depressed. This defective heart may result from the loss of cardiac pre-migratory neural crest cells. Taken together, we conclude that Arl6ip is not only required for neural crest specification, survival, and migration, but also for neural crest derivatives differentiation. This is the first report that demonstrates the in vivo function of Arl6ip during neural crest development.
| Identifer | oai:union.ndltd.org:TW/096NTU05061007 |
| Date | January 2008 |
| Creators | Tzu-Ching Yang, 楊子慶 |
| Contributors | Huai-Jen Tsai, 蔡懷楨 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 72 |
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