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Previous Article | Next Article
The Journal of Neuroscience, May 15, 2000, 20(10):3714-3724
Neuronal Basic Helix-Loop-Helix Proteins (NEX and BETA2/Neuro D) Regulate Terminal Granule Cell Differentiation in the Hippocampus
Markus H. Schwab1, Angelika Bartholomae1, Bernd Heimrich2, Dirk Feldmeyer3, Silke Druffel-Augustin1, Sandra Goebbels1, Frank J. Naya4, Shanting Zhao2, Michael Frotscher2, Ming-Jer Tsai4, and Klaus-Armin Nave1 1 Zentrum für Molekulare Biologie, University of Heidelberg, D-69120 Heidelberg, Germany, 2 Department of Anatomy, University of Freiburg, D-79001 Freiburg, Germany, 3 Max-Planck-Institut für Medizinische Forschung, Abteilung Zellphysiologie, D-69120 Heidelberg, Germany, and 4 Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030
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.
Key words: dentate gyrus; granule cells; neuronal differentiation factors; basic helix-loop-helix proteins; Cre recombination; Cajal-Retzius cells
Copyright © 2000 Society for Neuroscience 0270-6474/00/20103714-11$05.00/0
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