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Free keywords:
differentiation; Mash1; migration; neurogenesis; proliferation; Prox1
Abstract:
Dentate gyrus development is uniquely characterized by the existence of migrating precursors. The production of precursors by the neuroepithelium is regulated by the proneural cascade of bHLH genes, which show distinctive expression patterns in dentate. Mice carrying a mutation in Emx2, a neuroepithelial transcription factor, lack the granule cell layer which forms most of the dentate, although the corresponding neuroepithelium is correctly specified. To understand this phenotype, we have analyzed the expression of proneural genes (bHLH gene family) and other markers in Emx2-deficient dentate. Here we show that, in the mutant dentate, expression of bHLH genes, Tenascin C and GFAP is abnormally confined to the germinal layer, as are most neuronal and astrocytic precursors. Additionally, Mash1 expression (marker of migrating precursors) is lost during development. Mutant granule cells show arrested migration and lack NeuroD2 expression. These results are evidence that in Emx2 mutants, migrating precursors (secondary matrix) and astrocytes are absent, the radial migration substrate impaired and granule cells deficiently differentiated. Our analysis gives insight into how a general defect caused by the absence of Emx2 translates into the dentate-specific phenotype.
