細胞移動、層・神経核の形成 Cell Migration and Layer/Nuclear Formation

P3-1-64 大脳皮質ニューロンの移動と極性化における細胞質微小管の機能 Function of cytoplasmic microtubules in migration and polarization of neocortical neurons ○榊原明1, 安藤良太1, 夫馬裕太1, 野口奈美子1, 黒田麻衣子1, 正岡実1, 宮田卓樹1 ○Akira Sakakibara1, Ryota Ando1, Yuta Fuma1, Namiko Noguchi1, Maiko Kuroda1, Makoto Masaoka1, Takaki Miyata1 名古屋大学大学院 医学系研究科 細胞生物学1 Dept Anat Cell Biol, Nagoya Univ Grad Sch Med, Nagoya, Japan1 Neuronal migration and polarization require the proper organization and remodeling of cytoplasmic microtubules (MTs). To understand the mechanism by which MTs regulate neuronal migration and polarization, we performed loss of function experiments for MT binding proteins. Since we have successfully monitored dynamics of centrosome and MT plus ends in young migratory neurons in the developing mouse cerebrum, we applied this technology for analyses of neuronal phenotypes. Gamma-tubulin, a MT minus end binding protein, serves as a core of MT nucleation. Two genes (Tubg1 and Tubg2) encode functionally redundant gamma-tubulin proteins in mice. Therefore we used combination of Cre-mediated conditional knockout of Tubg1 and shRNA-mediated knockdown of Tubg2 in Tubg1 flox/flox mouse to deplete gamma-tubulin proteins in neocortical neurons. Early-onset phenotype of gamma-tubulin-depleted neurons is migration defect. These neurons stacked in the intermediate zone while keeping capability of forming axon-like fiber. A typical late-onset phenotype observed in the cortical plate is morphological abnormality in primary dendrite. Pia-oriented primary dendrites of gamma-tubulin-depleted neurons were thinner than control neurons. Live imaging of EB3-EGFP revealed that the density of growing MT plus ends in these thin processes was apparently low while the speed of MT growth was normal. Furthermore, aberrant behavior of centrosome in these cells was monitored by PACT-mKO1. XMAP215, which binds to tubulin heterodimer and MT plus end, regulates MT growth. XMAP215 shRNA-expressing neurons showed migration defect and stacked in the intermediate zone. These cells also exhibited abnormal axonogenesis.

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