• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Cell Migration and Layer/Nuclear Formation

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Pathophysiological roles of afadin in the brain development

  • P2-093
  • 山本 昆明 / Hideaki Yamamoto:1 萬代 研二 / Kenji Mandai:1 丸尾 知彦 / Tomohiko Maruo:1 今野 大治郎 / Daijiro Konno:2 松崎 文雄 / Fumio Matsuzaki:2 
  • 1:神戸大院・医・病態シグナル学 / Dept Med, Kobe Univ, Hyogo, Japan 2:理研CDB  / RIKEN CDB, Hyogo, Japan 

During the brain development, adherens junctions (AJs) of radial glial and ependymal cells and migration of neurons are essential for the formation and maintenance of the brain architecture. Afadin has been shown to regulate the formation of AJs and cell migration in epithelial cells. However, the role of afadin in the brain development in vivo is not fully understood. To address this question, we generated Nestin- and Emx1-Cre-mediated conditional afadin knockout (cKO) mice. The Nestin-Cre-mediated cKO mice developed hydrocephalus perinatally, resulting from stenosis of the caudal end of the cerebral aqueduct and obliteration of the ventral part of the third ventricle in the midbrain. In these mutant mice, AJs of radial glial and ependymal cells in the midbrain were disrupted. In contrast, the Emx1-Cre-mediated cKO mice caused double cortex formation, in which the heterotopic cortex was located underneath the normotopic cortex. The heterotopic cortex was disorganized, while the normotopic cortex was arranged in the six-layered pattern. In the afadin-deficient embryonic neocortex, AJs were disrupted in radial glial cells. In addition, knockdown of afadin in neurons of the wild-type neocortex impaired neuronal migration. Taken together, afadin is required for the maintenance of AJs in radial glial and ependymal cells and the cell-autonomous migration of neurons. Moreover, its deficiency in the midbrain and neocortex causes hydrocephalus and double cortex formation, respectively.

Copyright © Neuroscience2014. All Right Reserved.