Reelin regulates differentiation of neural stem cells by activation of notch signaling through Disabled-1 tyrosine phosphorylation

    Authors

    S. Keilani; D. Healey;K. Sugaya

    Comments

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    Abbreviated Journal Title

    Can. J. Physiol. Pharmacol.

    Keywords

    radial glia; NICD; DAB-1; neural progenitor; reelin; Notch; RADIAL GLIA DIFFERENTIATION; NEURONAL MIGRATION; PROTEIN; RECEPTORS; PATHWAY; KINASES; BINDING; TARGET; DAB1; Pharmacology & Pharmacy; Physiology

    Abstract

    We have previously reported the cross-talk between Reelin and Notch-1 signaling pathways, which are 2 major pathways that regulate brain development. We found that Reelin activated Notch-1 signaling, leading to the expression of brain lipid binding protein (BLBP) and the formation of radial glial cells in human neural progenitor cells (hNPCs). In the current study, we investigated the molecular mechanisms by which Reelin activates Notch-1. We show that Reelin-stimulated Notch-1 activation is dependent on Reelin signaling. The induction of Disabled-1 (Dab-1) tyrosine phosphorylation, and the subsequent activation of Src family kinases, were found to be essential steps for the activation of Notch-1 signaling by Reelin. Reelin treatment increased the interaction between Dab-1 and Notch-1 intracellular domain (NICD), and enhanced NICD translocation to the nucleus. This study advances our knowledge of the regulation of Notch-1 activation by Reelin signaling in hNPCs, as an approach to understanding cell fate determination, differentiation, and neurogenesis during brain development.

    Journal Title

    Canadian Journal of Physiology and Pharmacology

    Volume

    90

    Issue/Number

    3

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    361

    Last Page

    369

    WOS Identifier

    WOS:000301431400010

    ISSN

    0008-4212

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