Modulation of the notch signaling by Mash1 and Dlx1/2 regulates sequential specification and differentiation of progenitor cell types in the subcortical telencephalon.

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Basic-Helix-Loop-Helix-Transcription-Factors, Cell-Differentiation, DNA-Binding-Proteins, Down-Regulation, Gene-Expression-Regulation-Developmental, Genes-Homeobox, Homeodomain-Proteins, Membrane-Proteins, Mice, Mice-Inbred-C57BL, Mice-Mutant-Strains, Models-Neurological, Mutation, Phenotype, Receptors-Notch, Repressor-Proteins, Signal-Transduction, Stem-Cells, Telencephalon, Transcription-Factors

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Development 2002 Nov; 129(21):5029-40.


Notch signaling has a central role in cell fate specification and differentiation. We provide evidence that the Mash1 (bHLH) and Dlx1 and Dlx2 (homeobox) transcription factors have complementary roles in regulating Notch signaling, which in turn mediates the temporal control of subcortical telencephalic neurogenesis in mice. We defined progressively more mature subcortical progenitors (P1, P2 and P3) through their combinatorial expression of MASH1 and DLX2, as well as the expression of proliferative and postmitotic cell markers at E10.5-E11.5. In the absence of Mash1, Notch signaling is greatly reduced and 'early' VZ progenitors (P1 and P2) precociously acquire SVZ progenitor (P3) properties. Comparing the molecular phenotypes of the delta-like 1 and Mash1 mutants, suggests that Mash1 regulates early neurogenesis through Notch-and Delta-dependent and -independent mechanisms. While Mash1 is required for early neurogenesis (E10.5), Dlx1 and Dlx2 are required to downregulate Notch signaling during specification and differentiation steps of 'late' progenitors (P3). We suggest that alternate cell fate choices in the developing telencephalon are controlled by coordinated functions of bHLH and homeobox transcription factors through their differential affects on Notch signaling.

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