Journal
JOURNAL OF NEUROSCIENCE
Volume 20, Issue 10, Pages 3714-3724Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.20-10-03714.2000
Keywords
dentate gyrus; granule cells; neuronal differentiation factors; basic helix-loop-helix proteins; Cre recombination; Cajal-Retzius cells
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Funding
- NICHD NIH HHS [HD17379, R37 HD017379, R01 HD017379] Funding Source: Medline
- NIDDK NIH HHS [DK55325] Funding Source: Medline
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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.
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