Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells (Nat Neurosci, 2008, 11:440-449)

報告日期: 2008/12/05
報告時間: 16:00/16:50
報告學生: 謝崇斌
講評老師: 司君一

Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome
coupling in migrating granule cells

Nat Neurosci. 2008; 11(4):440-9


Speaker: Chung-Pin Hsieh (謝崇斌)

Commentator: Chun-I Sze, M.D. (司君一)

Date: 12/05 16:00-16:50



During brain development, granular cells migration in developing cerebellum provides a good model to discover the molecular mechanism of neuronal migration. Repetition of neurite elongation and soma translocation give rise to neuronal migration. During soma translocation, centrosome locates ahead of nucleus along the leading process and orients nucleus migrating forward (1). However, the mechanism of axon guidance molecules regulating soma translocation remains unclear. Previous study showed that Sema6A acts a ligand expressed in the cerebellar granular cells regulating the soma translocation during radial migration (2). However, the acted receptor of Sema6A regulating granular cell migration remains unclear. Plexin-A2 knockout mice showed abnormal migration of granular cells in cerebellum and inhibition of soma translocation observed in the cerebellar explants culture. NMF454 mice mutated by N-ethyl-N-nitrosourea had a single amino acid substitution of Plexin-A2 on the semaphorin domain and also showed the similar abnormal migration of granular cells in cerebellum. This mutation in the Plexin-A2 abolished the interaction with Sema6A, and mouse chimera of Plexin-A2 mouse showed the Plexin-A2 in the granular cell migration acts in a cell-autonomous manner supporting the relationship of ligand-receptor between Sema6A and Plexin-A2. In addition, using time lapse observing the migrating granular cells from cerebellar explants showed uncoupling and over-coupling of centrosome and nucleus in granular cells was found in Plexin-A2 and Sema6A knockout mice respectivly. In vivo study also showed that deposition of centrosome was also found in the ectopic granular cells in molecular layer of Plexin-A2 knockout mice. These results showed that sema6A-plexin-A2 signaling regulating cell migration by controlling centrosome positioning



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2.     Kerjan, G. et al. Nat. Neurosci. 8, 1516–1524 (2005).