title: Reelin regulates differentiation of neural stem cells by activation of notch signaling through Disabled-1 tyrosine phosphorylation.
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.
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827-7401, USA.
authors.forename: Serene
authors.initials: S
authors.lastname: Keilani
authors.forename: DeLacy
authors.initials: D
authors.lastname: Healey
authors.forename: Kiminobu
authors.initials: K
authors.lastname: Sugaya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D053829:Amyloid Precursor Protein Secretases / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis; D019000:Phosphotyrosine / Q000378:metabolism; D051881:Receptor, Notch1 / Q000502:physiology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015816:Cell Adhesion Molecules, Neuronal; C115785:DAB1 protein, human; D016326:Extracellular Matrix Proteins; C497761:NOTCH1 protein, human; D009419:Nerve Tissue Proteins; D051881:Receptor, Notch1; D000091042:Reelin Protein; D019000:Phosphotyrosine; D019061:src-Family Kinases; D053829:Amyloid Precursor Protein Secretases; C000717127:RELN protein, human; D012697:Serine Endopeptidases