Transcription factors of the basic Helix Loop Helix (bHLH) family play a central role in cell determination and differentiation of different cell types. NSCL-1 (neuronal stem cell leukemia) and NSCL-2 are two members of the bHLH family which are broadly expressed in different areas of the CNS and PNS during embryonic development and early postnatal stages. Based on their expression pattern a function as neuronal differentiation factors can be postulated. In order to understand the role of NSCL-1 and NSCL-2 during neurogenesis mouse strains containing targeted disruption of each gene were generated. Homozygous NSCL-1 deficient mice do not show any obvious phenotypic alterations. In contrast, NSCL-2-/- mutant mice show hypogonadism and adult onset of obesity. GnRH neurons are the main regulators of the reproductive system. Detailed morphometric and histochemical experiments revealed a significant reduction of GnRH positive neurons during peri- and postnatal stages. To address a putative cell autonomous role of NSCL-2 during the differentiation of the GnRH system, expression of NSCL-2 in GnRH neurons was analyzed. In addition, reduced expression of NPY Y1 receptors and POMC within the hypothalamus, which are important regulators for body weight control, was demonstrated. A detailed analysis of the major expression domains of NSCL-1 in particular the neocortex, and the cerebellum did not reveal any obvious morphological defects during development of these structures. Since NSCL-1 and NSCL-2 show overlapping spatiotemporal expression patterns, together with other bHLH genes, functional redundancy might be responsible for the lack of phenotypic alterations in NSCL-1-/- mice. To elucidate such compensatory effects, NSCL-1 and NSCL-2 double homozygous mutants were generated. Double homozygous mutants die within the first 24hr after birth. Despite the perinatal lethality, no obvious major malformation in the CNS were observed in double mutant mice. In contrast, the analysis of the olfactory epithelium of the double mutants displayed a reduced expression of pan-neuronal markers. In another attempt to characterize the function of NSCL-1 and NSCL-2, expression array analysis was used to identify transcripts with an altered abundancy in the NSCL-1xNSCL-2 double mutant mice. Changes in activity of genes which are involved in the regulation of apoptose and cell cycle suggest a role of NSCL-1 and NSCL-2 in these processes.