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The Journal of Neuroscience, February 15, 1998, 18(4):1408-1418
Neuronal Basic Helix-Loop-Helix Proteins (NEX, neuroD, NDRF):
Spatiotemporal Expression and Targeted Disruption of the NEX Gene in
Transgenic Mice
Markus H.
Schwab1,
Silke
Druffel-Augustin1,
Peter
Gass2,
Martin
Jung1,
Matthias
Klugmann1,
Angelika
Bartholomae1,
Moritz J.
Rossner1 and
Klaus-Armin
Nave1
1 Zentrum für Molekulare Biologie (ZMBH),
University of Heidelberg, D-69120 Heidelberg, Germany, and
2 Deutsches Krebsforschungszentrum, D-69120 Heidelberg,
Germany
Basic helix-loop-helix (bHLH) genes have emerged as important
regulators of neuronal determination and differentiation in vertebrates. Three putative neuronal differentiation factors [NEX for
neuronal helix-loop-helix protein-1 (mammalian atonal homolog-2), neuroD ( -2), and NDRF for neuroD-related factor (neuroD2)] are highly homologous to each other in the bHLH region and comprise a new
bHLH subfamily. To study the role of NEX, the first bHLH protein
identified in this group, we have disrupted the NEX gene by homologous
recombination. NEX-deficient mice have no obvious developmental defect,
and CNS neurons appear fully differentiated. To investigate further
whether the absence of NEX is compensated for by neuroD and NDRF, we
compared the spatiotemporal expression of all three genes. We
demonstrate, by in situ hybridization, that the
transcription patterns of NEX, neuroD, and NDRF genes are highly
overlapping in the developing CNS of normal rats between embryonic day
12 and adult stages but are not strictly identical. The most prominent
transcription of each gene marks the dorsal neuroepithelium of the
telencephalon in early development and is sustained in the adult
neocortex, hippocampus, and cerebellum. In general, neuroD provides the
earliest marker of neuronal differentiation in any given region
compared with NDRF or NEX. Whereas a few CNS regions are specific for
neuroD, no region was detected in which solely NEX or NDRF is
expressed. This suggests that the function of the mutant NEX gene in
neuronal differentiation is compensated for by neuroD and NDRF and
that, in analogy with myogenic bHLH proteins, neuronal differentiation
factors are at least in part equivalent in function.
Key words:
neuronal differentiation factors; forebrain development; basic helix-loop-helix proteins; neuroD; NDRF; NEX-1; homologous
recombination
Copyright © 1998 Society for Neuroscience 0270-6474/98/1841408-11$05.00/0
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