Unbound Ptc in the neural tube (left) leads to cell death.

Mehlen/AAAS

Without its partner, a lonely Sonic hedgehog (Shh) receptor chooses death, according to a report from Chantal Thibert, Patrick Mehlen (University of Lyon, Villeurbanne, France), and colleagues. This isolation-induced apoptosis prunes the developing neural tube.

Shh gradients along the ventral–dorsal axis of the neural tube direct neuronal differentiation via two transmembrane proteins: Patched (Ptc) and Smoothened (Smo). Removal of Shh during development is known to cause massive apoptosis in the neural tube, but this outcome was thought to be a byproduct of the failure of cells to differentiate. Mehlen's group now shows, however, that death is actively switched on by unbound Ptc.

Ptc expression in cultured cells induced apoptosis unless Shh was added. Similar results were seen with overexpression of Ptc in the neural tube. “Wherever Patched is expressed, those cells becomes dependent...

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