Desert hedgehog-patched 2 expression in peripheral nerves during Wallerian degeneration and regeneration

Abstract

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.

The Structural and Functional Integrity of Peripheral Nerves Depends on the Glial-Derived Signal Desert Hedgehog

“…3B), although there was a trend toward smaller diameters in dhhϪ/Ϫ nerves. This is in line with our previous light microscopic observations on myelinated units in dhhϪ/Ϫ and dhhϩ/ϩ nerves (Bajestan et al, 2006). There were no significant differences between dhhϩ/ϩ, dhhϩ/Ϫ, and dhhϪ/Ϫ nerves in the g-ratios of myelinated axons at any diameter This accords with previous light-microscopic measurements of average g-ratios in dhhϩ/ϩ and dhhϪ/Ϫ mice (Bajestan et al, 2006), indicating that although there are more incisures in dhhϪ/Ϫ nerves, the myelin thickness in most individual axons remains unaltered (Fig.…”

Patched2 Modulates Tumorigenesis in Patched1 Heterozygous Mice

“…The in situ hybridization analysis showed spatiotemporal differences between Ptch1 and Ptch2 expression, and so the nonoverlapping expression between these two proteins suggests that functional redundancy by Ptch1 does not account for normal development in the absence of Ptch2. Thus, Ptch1 and Ptch2 function differently during development, perhaps with Ptch2 fulfilling more subtle roles during SHH signaling, or Ptch2 participating more in other HH signaling pathways, such as Desert HH whose role in development is less critical than SHH (26,37,38).…”

Gpr126 is essential for peripheral nerve development and myelination in mammals

“…It is also possible that non-myelinating Schwann cells require a signal from promyelinating or myelinating Schwann cells that is altered in the absence of Gpr126; one such candidate signaling molecule is Dhh. Non-myelinating Schwann cells express the hedgehog receptor patched homolog 2 (Ptch2) in adult sciatic nerve and after injury (Bajestan et al, 2006). Although Dhh-Ptch2 signaling has not been directly shown to be required for the development of non-myelinating Schwann cells, Dhh mutant nerves possess significantly more axons sorted in a 1:1 relationship and fewer axons in Remak bundles , a pathology that is reminiscent of the defects observed in Gpr126-/-peripheral nerve.…”