deficiency of mdia, an actin nucleator, disrupts integrity of neuroepithelium and causes periventricular dysplasia肌动蛋白成核剂mdia不足,破坏神经上皮的完整性,引起室周的发育不良.pdfVIP

Deficiency of mDia, an Actin Nucleator, Disrupts Integrity of Neuroepithelium and Causes Periventricular Dysplasia 1 1 2 2 1 Dean Thumkeo , Ryota Shinohara , Keisuke Watanabe , Hirohide Takebayashi , Yosuke Toyoda , 1 1 1 1 Kiyoshi Tohyama , Toshimasa Ishizaki , Tomoyuki Furuyashiki , Shuh Narumiya * 1 Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, Japan, 2 Department of Morphological Neural Science, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Abstract During development of the central nervous system, the apical-basal polarity of neuroepithelial cells is critical for homeostasis of proliferation and differentiation of neural stem cells. While adherens junctions at the apical surface of neuroepithelial cells are important for maintaining the polarity, the molecular mechanism regulating integrity of these adherens junctions remains largely unknown. Given the importance of actin cytoskeleton in adherens junctions, we have analyzed the role of mDia, an actin nucleator and a Rho effector, in the integrity of the apical adherens junction. Here we show that mDia1 and mDia3 are expressed in the developing brain, and that mDia3 is concentrated in the apical surface of neuroepithelium. Mice deficient in both mDia1 and mDia3 develop periventricular dysplastic mass widespread throughout the developing brain, where neuroepithelial cell polarity is impaired with attenuated apical actin belts and loss of apical adherens junctions. In addition, electron microscopic analysis revealed abnormal shrinkage a