hedgehog proteins update

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J Neurobiol. 2005 Dec 2

Desert hedgehog-patched 2 expression in peripheral nerves during

Wallerian degeneration and regeneration.

Bajestan SN, Umehara F, Shirahama Y, Itoh K, Sharghi-Namini S, n

KR, Mirsky R, Osame M.

Department of Neurology and Geriatrics, Kagoshima University Graduate

School of Medical and Dental Sciences, Kagoshima, Japan.

Hedgehog proteins are important in the development of the nervous

system. As Desert hedgehog (Dhh) is involved in the development of

peripheral nerves and is expressed in adult nerves, it may play a

role in the maintenance of adult nerves and degeneration and

regeneration after injury. We firstly investigated the Dhh-receptors,

which are expressed in mouse adult nerves. The Dhh receptor patched

(ptc)2 was detected in adult sciatic nerves using RT-PCR, however,

ptc1 was undetectable under the same experimental condition. Using RT-

PCR in purified cultures of mouse Schwann cells and fibroblasts, we

found ptc2 mRNA in Schwann cells, and at much lower levels, in

fibroblasts. By immunohistochemistry, Ptc2 protein was seen on

unmyelinated nerve fibers. Then we induced crush injury to the

sciatic nerves of wild-type (WT) and dhh-null mice and the distal

stumps of injured nerves were analyzed morphologically at different

time points and expression of dhh and related receptors was also

measured by RT-PCR in WT mice. In dhh-null mice, degeneration of

myelinated fibers was more severe than in WT mice. Furthermore, in

regenerated nerves of dhh-null mice, minifascicular formation was

even more extensive than in dhh-null intact nerves. Both dhh and ptc2

mRNA levels were down-regulated during the degenerative phase

postinjury in WT mice, while levels rose again during the phase of

nerve regeneration. These results suggest that the Dhh-Ptc2 signaling

pathway may be involved in the maintenance of adult nerves and may be

one of the factors that directly or indirectly determines the

response of peripheral nerves to injury.