アクティブボード・２０１３年　５月
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研究発表を行った学会；
・“The Making of a Vertebrate” CDB symposium 2013
　２０１３年　３月　４日〜　６日（神戸）

タイトル；The apical endfoot of nascent neuron controls the pace pf neurogenesis though the regulation of Notch signaling.

発表者；畠山　淳　氏
　　　（熊本大学　発生医学研究所　脳発生分野）
Abstract；
Development of the vertebrate central nervous system (CNS) requires an exquisite balance between proliferation/self-renewal and differentiation of the neural progenitors. Notch signaling plays a pivotal role in regulating this balance, yet how signaling cells interact with receiving cells to turn on and off the signal.
We have shown that the adherens junction facilitates efficient interaction of Notch1 and Dll1 to maintain the undifferentiated state of the neural stem cells in the developing neural tube. In fact, disruption of AJs that are formed between apical endfeet of progenitors and nascent neurons resulted in aberrant and precocious neurogenesis that was preceded by the down-regulation of Notch signaling. Conversely, prolonged retention of the apical endfeet of neurons by stabilizing AJs caused delay in neuron production. Concerning the molecular mechanism by which the neuronal apical endfeet regulate neurogenesis, we provide several lines of evidence that adherens junctions facilitate Notch signaling. Notch1 and Dll1 form complex with the constituents of adherens junctions, such as ZO1 and cadherin. Moreover live imaging of a fluorescent tagged-Notch1 protein revealed its translocation from the apical endfeet to the nuclei.
Our results indicated that nascent neurons that express the ligands likely activate Notch signaling in neighboring progenitors at the apical endfeet to inhibit neural differentiation. We propose that the apical endfeet of neurons serve as a “pace-controller” for neurogenesis, thereby regulating histogenesis of the CNS tissues.