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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)

Functional importance of ADP-ribosylation factor 6 (Arf6) in the neuronal migration during cortical layer formation

  • P1-084
  • 原 芳伸 / Yoshinobu Hara:1 深谷 昌弘 / Masahiro Fukaya:1 阪上 洋行 / Hiroyuki Sakagami:1 
  • 1:北里大学 / Kitasato University School of Medicine Department of Anatomy 

Cortical layer formation in the cerebral cortex is one of the typical events in the mammalian brain. Neurons that are born in the ventricular zone migrate to the pial surface with an inside-out manner along the fiber of radial glia. Recent studies revealed that transmembrane proteins such as connexins, integrins, and N-cadherin, regulate neuronal migration through cell-cell and/or cell-matrix interactions, and their expression on the plasma membrane is tightly regulated by vesicle trafficking factors that are involved in the process of secretion, endocytosis and recycling. Furthermore, some vesicle trafficking factors are identified as a responsible gene for periventricular heterotopia, and their dysfunction causes malformation of cortical layer. However, it largely remains unclear the mechanistic details of how vesicle trafficking factors regulate neuronal migration. In this study, we examined the functional role of ADP-ribosylation factor 6 (Arf6), a critical regulator of endosomal trafficking, in the cortical layer formation. In situ hybridization analysis revealed that Arf6 mRNA was expressed in all layers including ventricular zone, intermediate zone, and cortical plate in the dorsal pallium of embryonic cerebral cortex. Furthermore, immunohistochemical analysis revealed that Arf6 appeared as puncta that partly colocalized with EEA1 and syntaxin12, markers for early and recycling endosomes, respectively, in migrating neurons. Knockdown of Arf6 by in utero electroporation resulted in the decrease in the cell population invading to layer II-IV. Furthermore, time-lapse observation demonstrated that neuronal migration was delayed in the intermediate zone by knockdown of Arf6. These results suggest that Arf6 regulates the neuronal migration through vesicle trafficking.

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