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Article

  • The EMBO Journal (2004) 23, 4353 - 4364
  • doi:10.1038/sj.emboj.7600431

Published online: 7 October 2004

NSCL-1 and NSCL-2 synergistically determine the fate of GnRH-1 neurons and control necdin gene expression

Marcus Krügera, Karen Ruschkea and Thomas Braun

  1. Institute of Physiological Chemistry, University of Halle-Wittenberg, Halle, Germany

Correspondence to:

Thomas Braun, Institut f. Physiologische Chemie, Martin-Luther-Universität, Halle-Wittenberg, Hollystr. 1, Halle, 06097, Germany. Tel.: +49 345 557 3813; Fax: +49 345 557 3811; E-mail: thomas.braun@medizin.uni-halle.de

aThese authors contributed equally to this work

Received 14 April 2004; Accepted 7 September 2004

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.

  • Keywords:

    • differentiation,
    • migration,
    • Prader–Willi syndrome