A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of Sonic hedgehog in the neural tube

Cell pattern in the ventral neural tube is organized by Sonic hedgehog (Shh) secreted by floor plate cells. To assay the range of direct Shh action, we developed a general method for blocking transduction of Hedgehog (Hh) signals through ectopic expression of a deleted form of the Hh receptor Patched (Ptc), termed Ptc(Delta loop2). We validated this method in Drosophila and used mouse Ptc(Delta loop2) (mPtc1(Delta loop2)) to block Shh transduction in the chick neural tube. mPtc1(Delta loop2) expression caused cell-autonomous ventral-to-dorsal switches in progenitor identity and neuronal fate throughout the ventral neural tube, supporting a gradient mechanism whereby Shh acts directly and at long range. mPtc1(Delta looP2) expression also caused the abnormal spread of Shh to more dorsal cells, indicating that Shh in the neural tube, like Hh in Drosophila, induces a feedback mechanism that limits its range of action.