Regulation of neural progenitor cell motility by ceramide and potential implications for mouse brain development.
Regulation of neural progenitor cell motility by ceramide and potential implications for mouse brain development.
复制标题
神经酰胺对神经祖细胞运动的调节及其对小鼠大脑发育的潜在影响。
DOI：
10.1111/j.1471-4159.2008.05451.x
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发表时间：
2008
影响因子：
4.7
通讯作者：
Bieberich,Erhard
中科院分区：
文献类型：
--
作者：
Wang,Guanghu;Krishnamurthy,Kannan;Chiang,Ying-Wei;Dasgupta,Somsankar;Bieberich,Erhard
We provide evidence that the sphingolipid ceramide, in addition to its pro‐apoptotic function, regulates neural progenitor (NP) motilityin vitroand brain developmentin vivo. Ceramide (N‐palmitoyld‐erythro sphingosine andN‐oleoyld‐erythro sphingosine) and the ceramide analogN‐oleoyl serinol (S18) stimulate migration of NPs in scratch (wounding) migration assays. Sphingolipid depletion by inhibition ofde novoceramide biosynthesis, or ceramide inactivation using an anti‐ceramide antibody, obliterates NP motility, which is restored by ceramide or S18. These results suggest that ceramide is crucial for NP motility. Wounding of the NP monolayer activates neutral sphingomyelinase indicating that ceramide is generated from sphingomyelin. In membrane processes, ceramide is co‐distributed with its binding partner atypical protein kinase C ζ/λ (aPKC), and Cdc42, α/β‐tubulin, and β‐catenin, three proteins involved in aPKC‐dependent regulation of cell polarity and motility. Sphingolipid depletion by myriocin prevents membrane translocation of aPKC and Cdc42, which is restored by ceramide or S18. These results suggest that ceramide‐mediated membrane association of aPKC/Cdc42 is important for NP motility.In vivo, sphingolipid depletion leads to ectopic localization of mitotic or post‐mitotic neural cells in the embryonic brain, while S18 restores the normal brain organization. In summary, our study provides novel evidence that ceramide is critical for NP motility and polarityin vitroandin vivo.
