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The structural and functional integrity of peripheral nerves depends on the glial-derived signal desert hedgehog

Sharghi-Namini, S; Turmaine, M; Meier, C; Sahni, V; Umehara, F; Jessen, KR; Mirsky, R; (2006) The structural and functional integrity of peripheral nerves depends on the glial-derived signal desert hedgehog. J NEUROSCI , 26 (23) 6364 - 6376. 10.1523/JNEUROSCI.0157-06.2006. Green open access

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Abstract

We show that desert hedgehog ( dhh), a signaling molecule expressed by Schwann cells, is essential for the structural and functional integrity of the peripheral nerve. Dhh-null nerves display multiple abnormalities that affect myelinating and nonmyelinating Schwann cells, axons, and vasculature and immune cells. Myelinated fibers of these mice have a significantly increased ( more than two times) number of Schmidt-Lanterman incisures ( SLIs), and connexin 29, a molecular component of SLIs, is strongly upregulated. Crossing dhh-null mice with myelin basic protein ( MBP)-deficient shiverer mice, which also have increased SLI numbers, results in further increased SLIs, suggesting that Dhh and MBP control SLIs by different mechanisms. Unmyelinated fibers are also affected, containing many fewer axons per Schwann cell in transverse profiles, whereas the total number of unmyelinated axons is reduced by approximately one-third. In dhh-null mice, the blood-nerve barrier is permeable and neutrophils and macrophage numbers are elevated, even in uninjured nerves. Dhh-null nerves also lack the largest-diameter myelinated fibers, have elevated numbers of degenerating myelinated axons, and contain regenerating fibers. Transected dhh nerves degenerate faster than wild-type controls. This demonstrates that a single identified glial signal, Dhh, plays a critical role in controlling the integrity of peripheral nervous tissue, in line with its critical role in nerve sheath development ( Parmantier et al., 1999). The complexity of the defects raises a number of important questions about the Dhh-dependent cell-cell signaling network in peripheral nerves.

Type: Article
Title: The structural and functional integrity of peripheral nerves depends on the glial-derived signal desert hedgehog
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.0157-06.2006
Keywords: glia, degeneration, regeneration, hedgehog, PNS, electron microscopy, neuropathy, MYELINATING SCHWANN-CELLS, SCHMIDT-LANTERMAN INCISURES, RAT SCIATIC-NERVE, WALLERIAN DEGENERATION, SONIC HEDGEHOG, SYNAPTIC-TRANSMISSION, DIABETIC-NEUROPATHY, GENE-EXPRESSION, TIGHT JUNCTIONS, GAP-JUNCTIONS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10592
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