Title

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

Authors

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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