Exploring Cues Regulating the Polarity of Radial Glial

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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.