Fig. 7. Models showing progenitor cell (P) and neuronal (N) maturation in the LGE of wild-type, Mash1^-/-, Dll1^-/- and Dlx1/2^-/- embryos. MASH1-/DLX2- neuroepithelial progenitors (P1) give rise to MASH1+/DLX2- (P2) and MASH1+/DLX2+ (P3) progenitors around E10. An alternate model would have P1 cells separately generate P2 and P3 states. Lineage analysis will be needed to determine the relationships between the postulated progenitor cells and their derivatives. We propose that P2 cells mature into early neurons (N1), while P3 cells proliferate to form the SVZ progenitor zone and produce later-born neurons (N2). Mash1 is required cell-autonomously to specify P2 progenitors and hence N1 neurons. Mash1 is also required non cell-autonomously: increasing Dll1 expression to prevent neighboring cells from acquiring the P3 fate prematurely via Notch-dependent lateral inhibition. In Dll1 mutants, P1, P2 and P3 progenitors are present, but their maturation is accelerated due to decreased Notch signaling. By contrast, early neurogenesis is normal in the Dlx1/2 mutants but P3 progenitors are blocked in their ability to differentiate. This phenotype is attributed to the failure to downregulate Notch signaling during specification and/or differentiation steps of P3 maturation. The arrows between cell states do not necessarily imply that mitosis is required. The enlarged arrows represent hypothesized increases in the rate of the indicated process.

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