Schwann cell-derived desert hedgehog controls the development of peripheral nerve sheaths

We show that Schwann cell-derived Desert hedgehog (Dhh) signals the formati on of the connective tissue sheath around peripheral nerves, mRNAs for dhh and its receptor patched (ptc) are expressed in Schwann cells and perineura l mesenchyme, respectively. In dhh(-/-) mice, epineurial collagen is reduce d, while the perineurium is thin and disorganized, has patchy basal lamina, and fails to express connexin 43. Perineurial tight junctions are abnormal and allow the passage of proteins and neutrophils. In nerve fibroblasts, D hh upregulates ptc and hedgehog-interacting protein (hip). These experiment s reveal a novel developmental signaling pathway between glia and mesenchym al connective tissue and demonstrate its molecular identity in peripheral n erve. They also show that Schwann cell-derived signals can act as important regulators of nerve development.