The Neuronal Basic Helix-Loop-Helix Transcription Factor NSCL-1 Is Dispensable for Normal Neuronal Development

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Abstract
The neuronal stem cell leukemia (NSCL) basic helix-loop-helix factors are neural cell-specific transcription factors. We have disrupted the NSCL-1 gene by homologous recombination and replaced the coding region with a beta-galactosidase reporter cassette to study the role of NSCL-1 in neuronal development and to follow the fate of NSCL-1 mutant cells. NSCL-1 mutant mice are viable and fertile on various genetic backgrounds and do not show any obvious signs of neurological malfunction. No differences in the distribution of NSCL-1 mutant or heterozygous neuronal cells were observed in the diencephalon, hippocampus, neocortex, and cerebellum at different stages of development. Likewise, no defects were found in the laminar organization of the cortex, and the distinct neuronal subpopulation appeared normal during development of the neocortex. Analysis of sensory neurons which strongly express NSCL-1 revealed that the spatiotemporal expression of neuronal differentiation factors, such as NeuroD and SCG-10, was not altered in developing distal and proximal cranial ganglia of mutant mice. In the cerebellum expression of NSCL-1 was confined to the proliferative and premigratory zone of the external granular layer and the internal granular layer. Interestingly, unlike cerebella of Math1−/− or NeuroD2−/− mice, NSCL-1-deficient mice have no obvious developmental defect, and neurons of the cerebellum appeared fully differentiated. Despite similar expression patterns of NSCL-1 and NSCL-2 in various areas of the diencephalon, including the arcuate nucleus and paraventricular nucleus, NSCL-1−/− mice are fertile and show no adult onset of obesity like NSCL-2 mutant mice. Double-mutant NSCL-1−/−-NSCL-2−/− mice do not show any additional obvious malformations of the central nervous system, although both genes are expressed in a largely overlapping pattern. Our results argue against a simple functional redundancy within the NSCL gene family.