| First Author | Krüger M | Year | 2004 |
| Journal | EMBO J | Volume | 23 |
| Issue | 21 | Pages | 4353-64 |
| PubMed ID | 15470499 | Mgi Jnum | J:93303 |
| Mgi Id | MGI:3056835 | Doi | 10.1038/sj.emboj.7600431 |
| Citation | Kruger M, et al. (2004) NSCL-1 and NSCL-2 synergistically determine the fate of GnRH-1 neurons and control necdin gene expression. EMBO J 23(21):4353-64 |
| abstractText | To study the role of the bHLH genes NSCL-1 and NSCL-2 in the development of GnRH-1 neurons, we have generated compound mutant mice. Mutant animals die at birth and show a virtually complete absence of GnRH-1 neurons in the posterior parts of the brain at E18.5 and an aberrant morphology of the remaining GnRH-1 neurons in the anterior parts of the brain indicating that NSCL-1 and NSCL-2 might concomitantly control differentiation/migration of GnRH-1 neurons in a cell autonomous manner. To gain further insights into this process, we screened for NSCL target genes using DNA array hybridization and detected necdin, which is deleted in the human Prader-Willi syndrome phenotypically resembling the NSCL-2 mutation. Using chromatin immunoprecipitation and site-directed mutagenesis of the necdin promoter, we demonstrate that NSCLs together with additional cofactors directly control transcription of the necdin gene. NSCL-dependent control of necdin expression might be instrumental for proper neuronal cell differentiation and enable GnRH-1 neurons to migrate. |
