A MAMMALIAN PATCHED HOMOLOG IS EXPRESSED IN TARGET TISSUES OF SONIC HEDGEHOG AND MAPS TO A REGION ASSOCIATED WITH DEVELOPMENTAL ABNORMALITIES

Drosophila patched is a segment polarity gene required for the correct patterning of larval segments and imaginal discs during fly developme nt and has a close functional relationship with hedgehog. We have isol ated a complete human PATCHED cDNA sequence, which encodes a putative protein of 1296 amino acids, and displays 39% identity and 60% similar ity to the Drosophila PATCHED protein, Hydropathy analysis suggests th at human PATCHED is an integral membrane protein with a pattern of hyd rophobic and hydrophilic stretches nearly identical to that of Drosoph ila patched, In the developing mouse embryo, patched is initially dete cted within the ventral neural tube and later in the somites and limb buds, Expression in the limb buds is restricted to the posterior ectod erm surrounding the zone of polarizing activity, The results show that patched is expressed in target tissues of sonic hedgehog, a murine ho molog of Drosophila hedgehog suggesting that patched/hedgehog interact ions have been conserved during evolution. Human PATCHED maps to human chromosome 9q22.3, the candidate region for the nevoid basal cell car cinoma syndrome. Patched expression is compatible with the congenital defects observed in the nevoid basal cell carcinoma syndrome.