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XB-ART-11038
J Neurosci May 15, 2000; 20 (10): 3714-24.
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Neuronal basic helix-loop-helix proteins (NEX and BETA2/Neuro D) regulate terminal granule cell differentiation in the hippocampus.

Schwab MH , Bartholomae A , Heimrich B , Feldmeyer D , Druffel-Augustin S , Goebbels S , Naya FJ , Zhao S , Frotscher M , Tsai MJ , Nave KA .


Abstract
The transcription factors neuronal helix-loop-helix protein (NEX)/mammalian atonal homolog 2 (Math-2), BETA2/neuronal determination factor (NeuroD), and NeuroD-related factor (NDRF)/NeuroD2 comprise a family of Drosophila atonal-related basic helix-loop-helix (bHLH) proteins with highly overlapping expression in the developing forebrain. The ability of BETA2/NeuroD and NDRF to convert ectodermal cells into neurons after mRNA injection into Xenopus oocytes suggested a role in specifying neuronal cell fate. However, neuronal bHLH genes are largely transcribed in CNS neurons, which are fully committed. Here we analyze a defect in mice lacking BETA2/NeuroD, and in NEX*BETA2/NeuroD double mutants, demonstrating that bHLH proteins are required in vivo for terminal neuronal differentiation. Most strikingly, presumptive granule cells of the dentate gyrus are generated but fail to mature, lack normal sodium currents, and show little dendritic arborization. Long-term hippocampal slice cultures demonstrate secondary alterations of entorhinal and commissural/associational projections. The primary developmental arrest appears to be restricted to granule cells in which an autoregulatory system involving all three neuronal bHLH genes has failed.

PubMed ID: 10804213
PMC ID: PMC6772686
Article link: J Neurosci
Grant support: [+]

Species referenced: Xenopus
Genes referenced: neurod1

References [+] :
Adams, Heavy metal intensification of DAB-based HRP reaction product. 1981, Pubmed