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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
.
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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.
Adams,
Heavy metal intensification of DAB-based HRP reaction product.
1981, Pubmed
Adams,
Heavy metal intensification of DAB-based HRP reaction product.
1981,
Pubmed
Ahmad,
The role of NeuroD as a differentiation factor in the mammalian retina.
1998,
Pubmed
Akagi,
Cre-mediated somatic site-specific recombination in mice.
1997,
Pubmed
Altman,
Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods.
1990,
Pubmed
Altman,
Mosaic organization of the hippocampal neuroepithelium and the multiple germinal sources of dentate granule cells.
1990,
Pubmed
Arnold,
Muscle differentiation: more complexity to the network of myogenic regulators.
1998,
Pubmed
Barami,
Hu protein as an early marker of neuronal phenotypic differentiation by subependymal zone cells of the adult songbird forebrain.
1995,
Pubmed
Bartholomä,
NEX-1: a novel brain-specific helix-loop-helix protein with autoregulation and sustained expression in mature cortical neurons.
1994,
Pubmed
Connors,
Intrinsic firing patterns of diverse neocortical neurons.
1990,
Pubmed
Deller,
The hippocampus of the reeler mutant mouse: fiber segregation in area CA1 depends on the position of the postsynaptic target cells.
1999,
Pubmed
Frotscher,
Development of identified neuronal types and of specific synaptic connections in slice cultures of rat hippocampus.
1995,
Pubmed
Gerlach,
Ki-67 expression during rat liver regeneration after partial hepatectomy.
1997,
Pubmed
Halevy,
Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD.
1995,
Pubmed
Horikawa,
A versatile means of intracellular labeling: injection of biocytin and its detection with avidin conjugates.
1988,
Pubmed
Kageyama,
Helix-loop-helix factors in growth and differentiation of the vertebrate nervous system.
1997,
Pubmed
Kume,
Molecular cloning of a novel basic helix-loop-helix protein from the rat brain.
1996,
Pubmed
Lassar,
Regulatory mechanisms that coordinate skeletal muscle differentiation and cell cycle withdrawal.
1994,
Pubmed
Lee,
Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein.
1995,
Pubmed
,
Xenbase
Lee,
Basic helix-loop-helix genes in neural development.
1997,
Pubmed
Ma,
Identification of neurogenin, a vertebrate neuronal determination gene.
1996,
Pubmed
,
Xenbase
Malecki,
Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus.
1999,
Pubmed
McCormick,
NeuroD2 and neuroD3: distinct expression patterns and transcriptional activation potentials within the neuroD gene family.
1996,
Pubmed
,
Xenbase
Miyata,
NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus.
1999,
Pubmed
Morrow,
NeuroD regulates multiple functions in the developing neural retina in rodent.
1999,
Pubmed
Naya,
Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice.
1997,
Pubmed
Naya,
Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor.
1995,
Pubmed
Pellegrini,
Dentate gyrus formation requires Emx2.
1996,
Pubmed
Schwab,
Neuronal basic helix-loop-helix proteins (NEX, neuroD, NDRF): spatiotemporal expression and targeted disruption of the NEX gene in transgenic mice.
1998,
Pubmed
Schwegler,
Strain-specific development of the mossy fiber system in organotypic cultures of the mouse hippocampus.
1988,
Pubmed
Shimizu,
MATH-2, a mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal, is specifically expressed in the nervous system.
1995,
Pubmed
Sommer,
neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination genes that reveal progenitor cell heterogeneity in the developing CNS and PNS.
1996,
Pubmed
,
Xenbase
Stanfield,
The development of the hippocampus and dentate gyrus in normal and reeler mice.
1979,
Pubmed
Stoppini,
A simple method for organotypic cultures of nervous tissue.
1991,
Pubmed
Thayer,
Positive autoregulation of the myogenic determination gene MyoD1.
1989,
Pubmed
Yan,
neuroD induces photoreceptor cell overproduction in vivo and de novo generation in vitro.
1998,
Pubmed
Yasunami,
Molecular cloning and characterization of a cDNA encoding a novel basic helix-loop-helix protein structurally related to Neuro-D/BHF1.
1996,
Pubmed
Yoon,
Molecular cloning and characterization of the gene encoding human NeuroD.
1998,
Pubmed
Yoshida,
Emx1 and Emx2 functions in development of dorsal telencephalon.
1997,
Pubmed
Zhao,
Control of hippocampal morphogenesis and neuronal differentiation by the LIM homeobox gene Lhx5.
1999,
Pubmed