Flanking regulatory sequences of the locus encoding the murine GDNF receptor, c-ret, directs Lac Z (beta-galactosidase) expression in developing somatosensory system

RET forms the catalytic component within the receptor complex that transmit s signals from the GDNF family of neurotrophic factors. To study the mechan isms regulating the cell-type specific expression of this gene, we have clo ned and characterised the murine c-ret locus. A cosmid contig comprising ap proximately 60 kb of the mouse genome encompassing the entire structural ge ne and flanking sequences have been isolated and the transcription initiati on site identified and promoter characterised. The murine c-ret promoter la cks a TATA initiation motif and has GC enriched DNA sequences reminiscent o f CpG islands. Analysis of transgenic mice lines bearing the Lac Z (beta -g alactosidase) reporter gene under the control of 5' flanking sequences show modularity in the organisation of cis-regulatory domains within the locus. Cloned 5' flanking sequences comprise a distal regulatory domain directing Lac Z expression at the primitive streak, lateral mesoderm and facial gang lia and a proximal sensory neurones specific regulatory domain inducing Lac Z expression primarily within the developing somatosensory system. The spa tial and temporal progression of transgene expression precisely recapitulat es endogenous gene expression in developing sensory ganglia including its i nduction in postnatal Isolectin B4 binding nociceptive neurones. (C) 2001 W iley-Liss, Inc.