Exploring Cues Regulating the Polarity of Radial Glial

描述（由申请人提供）：放射状神经胶质细胞对于哺乳动物脑的正确形成至关重要，既提供了新神经元的来源，又提供了神经元迁移的支架。这些功能依赖于放射状胶质细胞的结构和分子极性，并且在其发育、分化和神经元相互作用的任何方面的破坏都可能导致脑内细胞的异常放置。放射状胶质细胞是发育中的神经系统中最显著极化的细胞之一，这种极性的破坏可导致脑内的严重畸形，如无脑回畸形、多小脑回畸形和异位畸形。为了探索这些细胞中极性的调节，我们专注于神经调节蛋白1（NRG 1）及其受体ErbB调节的分子信号传导事件。特别是，已经建立，通过这种受体复合物的信号是重要的，在建立和维持放射状胶质细胞内的极性，我们将确定是否激活细胞极性的主要决定因素通过ErbB信号调节。此外，我们将调查是否诱导ErbB2在成年人的大脑是足以恢复星形胶质细胞放射状胶质细胞。这些分子事件的研究将大大有助于了解哺乳动物的大脑发育。

DESCRIPTION (provided by applicant): Radial glial cells are critical for the proper formation of the mammalian brain, providing both a source of new neurons as well as a scaffold for neuronal migration. These functions of depend on the structural and molecular polarity of radial glia and disruption in any aspect of their development, differentiation, and neuronal interaction can lead to aberrant placement of cells within the brain. Radial glia are one of the most strikingly polarized cells in the developing nervous system and disruption in this polarity can result in gross malformation within the brain, such as lissencephaly, polymicrogyria, and heterotopias. To explore the regulation of polarity in these cells, we have focused on molecular signaling events regulated by neuregulin 1 (NRG1) and its receptor, ErbB. In particular, having established that signaling through this receptor complex is important in establishing and maintaining polarity within radial glial cells, we will determine whether activation of principal determinants in cell polarity are regulated through ErbB signaling. Furthermore, we will investigate whether induction of ErbB2 in the adult brain is sufficient to revert astrocytes to radial glia. Study of these molecular events will significantly contribute to understanding of mammalian brain development.