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[P2.13]: BDNF promoter‐IV knock‐in mice as a novel animal model for studying shared mechanisms of Rett and autism
Author(s) -
Sun J.X.,
Zhang Z.,
Zhang C.,
Sakata K.,
Lu B.,
Sun Q.Q.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.143
Subject(s) - zhàng , library science , citation , physics , political science , computer science , law , china
chick oculomotor system has a precocious development, ease of accessibility for manipulation and homology to the human pattern of innervation which make it ideal for investigating fundamental aspects of neurobiology and human congenital disorders, notably strabismus. Drebrin is required for neuritogenesis and potently induces filopodia. Oculomotor leading processes are enriched in drebrin and RNAi-mediated knockdown of drebrin blocks leading process formation and neuronal migration. Conversely, overexpression of drebrin induces premature migration, midline repulsion of leading processes and dramatic deviations in trajectory. Nck2 contains SH2 and SH3 domains and is known to bind several axon guidance receptors, potentially coupling them to cytoskeletal effectors. We show that drebrin specifically binds Nck2 but not the closely related Nck1, furthermore Drebrin and Nck2 colocalise at the leading edge of growth cones. This appears to be a competitive interaction: overexpression of Nck2 had the same effect as loss of drebrin, no leading processes were formed and the cells failed to migrate. We propose that the binding of Nck2 to drebrin is modulated by the activity of extracellular receptors in order to promote or inhibit actin filament formation as appropriate.