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Cell Migration and Layer/Nuclear Formation

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

Analysis of the intramolecular regulatory mechanism of Dab1 in the developing neocortex

  • P1-082
  • 並河 知宏 / Tomohiro Namikawa:1 寺島 俊雄 / Toshio Terashima:1 吉川 知志 / Satoshi Kikkawa:1 
  • 1:神戸大院・医・生理学・細胞生物学・神経発生 / Div of Dev Neurobiol, Kobe Univ Grad Sch of Med, Hyogo, Japan 

Neurons in the developing mammalian neocortex form a laminar structure in an "inside-out" manner. This layered structure is established by coordinated neuronal migration regulated by several signaling cascades, including the Reelin-Dab1 pathway. When Reelin binds to its receptors, ApoER2 and VLDLR, Dab1 is tyrosine-phosphorylated by Src family kinases and regulates downstream effectors. We have previously investigated the effects of various truncated forms of Dab1 on the morphology of transfected cells and postulated a possible intramolecular regulatory mechanism between the N-terminal (Nt) and C-terminal (Ct) domains within Dab1. To further investigate this hypothesis, we expressed the various Dab1 fragments in migrating neocortical neurons by in utero electroporation and examined neuronal migration of the transfected neurons. When electroporated with the full-length Dab1 construct, together with an EGFP reporter, at embryonic day 14.5, the labeled cells generally showed a dispersed distribution spanning the entire cortical plate. On the other hand, the cortical neurons electroporated with the Nt construct highly accumulated in the lower cortical plate. The same phenotype was observed when electroporated with the shorter Nt fragment which lacks the phosphotyrosine domain. Interestingly, when each Nt fragment was co-electroporated with the complementary Ct fragment, the number of cells ectopically accumulating in the lower cortical plate decreased and that of the cells which migrated to the upper position of the cortical plate increased. These results suggest that the intramolecular interaction between the Nt and Ct domains within the Dab1 protein regulates its function in the migrating neurons in the developing neocortex.

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