Overexpression of ptc1 inhibits induction of Shh target genes and preventsnormal patterning in the neural tube

Patched (Ptc) is a human tumor suppressor protein and a candidate receptor for Hedgehog (Hh) proteins, which regulate growth and patterning in embryos . Ptc represses expression of Hh target genes such as Gli1 and ptc1 itself. Localized secretion of Hh appears to induce transcription of target genes in specific patterns by binding to Ptc and preventing it from functioning i n recipient cells. People who are heterozygous for PTC1 exhibit a range of developmental defects, suggesting that some genes are inappropriately expre ssed when there is not enough Ptc protein. To test the idea that a balance between Hh and Ptc activities is essential for normal development, we overe xpressed Ptc in the neural tube. We find that excess Ptc is sufficient to i nhibit expression of Gli1 and ptc1, suggesting that Sonic hedgehog (Shh) ca nnot signal effectively. This leads to partial dorsalization of the neural tube and a wide: spectrum of neural defects, ranging from embryonic lethali ty to hydrocephaly. (C) 1999 Academic Press.