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• W2032912688 abstract "Neurod1 is a crucial basic helix-loop-helix gene for most cerebellar granule cells and mediates the differentiation of these cells downstream of Atoh1-mediated proliferation of the precursors. In Neurod1 null mice, granule cells die throughout the posterior two thirds of the cerebellar cortex during development. However, Neurod1 is also necessary for pancreatic β-cell development, and therefore Neurod1 null mice are diabetic, which potentially influences cerebellar defects. Here, we report a new Neurod1 conditional knock-out mouse model created by using a Tg(Atoh1-cre) line to eliminate Neurod1 in the cerebellar granule cell precursors. Our data confirm and extend previous work on systemic Neurod1 null mice and show that, in the central lobules, granule cells can be eradicated in the absence of Neurod1. Granule cells in the anterior lobules are partially viable and depend on as yet unknown genes, but the Purkinje cells show defects not previously recognized. Interestingly, delayed and incomplete Tg(Atoh1-cre) upregulation occurs in the most posterior lobules; this leads to near normal expression of Neurod1 with a concomitant normal differentiation of granule cells, Purkinje cells, and unipolar brush cells in lobules IX and X. Our analysis suggests that Neurod1 negatively regulates Atoh1 to ensure a rapid transition from proliferative precursors to differentiating neurons. Our data have implications for research on medulloblastoma, one of the most frequent brain tumors of children, as the results suggest that targeted overexpression of Neurod1 under Atoh1 promoter control may initiate the differentiation of these tumors." @default.
• W2032912688 created "2016-06-24" @default.
• W2032912688 creator A5050109541 @default.
• W2032912688 creator A5055075998 @default.
• W2032912688 creator A5067816966 @default.
• W2032912688 creator A5078729975 @default.
• W2032912688 date "2009-07-17" @default.
• W2032912688 modified "2023-10-10" @default.
• W2032912688 title "Defects in the cerebella of conditional Neurod1 null mice correlate with effective Tg(Atoh1-cre) recombination and granule cell requirements for Neurod1 for differentiation" @default.
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• W2032912688 doi "https://doi.org/10.1007/s00441-009-0826-6" @default.
• W2032912688 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3023111" @default.
• W2032912688 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19609565" @default.
• W2032912688 hasPublicationYear "2009" @default.
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