
doi: 10.1139/y2012-001
pmid: 22394407
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.
Silicon, Notch, neural progenitor, DAB1, Physiology, Cell Adhesion Molecules, Neuronal, Neurogenesis, radial glia, PROTEIN, Nerve Tissue Proteins, PATHWAY, NICD, Neural Stem Cells, Orientation, reelin, BINDING, Oxidation, Humans, Cell Lineage, Pharmacology & Pharmacy, Receptor, Notch1, Phosphotyrosine, Cells, Cultured, Adaptor Proteins, Signal Transducing, Extracellular Matrix Proteins, Nanowires, KINASES, Serine Endopeptidases, Cell Differentiation, DAB-1, RECEPTORS, Reelin Protein, TARGET, HEK293 Cells, src-Family Kinases, NEURONAL MIGRATION, RADIAL GLIA DIFFERENTIATION, Amyloid Precursor Protein Secretases, Signal Transduction
Silicon, Notch, neural progenitor, DAB1, Physiology, Cell Adhesion Molecules, Neuronal, Neurogenesis, radial glia, PROTEIN, Nerve Tissue Proteins, PATHWAY, NICD, Neural Stem Cells, Orientation, reelin, BINDING, Oxidation, Humans, Cell Lineage, Pharmacology & Pharmacy, Receptor, Notch1, Phosphotyrosine, Cells, Cultured, Adaptor Proteins, Signal Transducing, Extracellular Matrix Proteins, Nanowires, KINASES, Serine Endopeptidases, Cell Differentiation, DAB-1, RECEPTORS, Reelin Protein, TARGET, HEK293 Cells, src-Family Kinases, NEURONAL MIGRATION, RADIAL GLIA DIFFERENTIATION, Amyloid Precursor Protein Secretases, Signal Transduction
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