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The Journal of Neuroscience, July 9, 2003, 23(14):6132-6140

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Sequential Signaling through Notch1 and erbB Receptors Mediates Radial Glia Differentiation

Brooke A. Patten,¹ Jean Michel Peyrin,¹ Gerry Weinmaster,² and Gabriel Corfas¹

¹Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, and ²Department of Biological Chemistry, University of California Los Angeles School of Medicine, Los Angeles, California 90095-1737

Radial glia cells both generate neurons and physically guide nascent neurons to their target destination in the cortex, and as such they are essential for CNS development. It has been proposed that in the developing cerebellum, neuronal contact induces radial glia formation, however, the mechanisms involved in this process are not well understood. Here we demonstrate that neuronal induction of radial glia formation is the result of sequential signaling through Notch1 and erbB receptors. First, Notch1 activation by neuronal contact induces the glial expression of the brain lipid binding protein (BLBP) and erbB2 genes. Interestingly, two different signaling pathways mediate these effects of Notch1 on transcription, BLBP expression being dependent on Su(H), whereas erbB2 is regulated by a yet unidentified Notch1 pathway. The subsequent increase in erbB2 receptor expression makes the glia more responsive to neuronal NRG, which then induces the morphological transformation into radial glia. Thus, these results unveil some of the mechanisms underlying radial glia formation.

Key words: Notch1; Su(H); erbB; cerebellum; glia; BLBP

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Received Mar. 19, 2003; revised May. 13, 2003; accepted May. 16, 2003.

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