Premium
Hedgehog Proteins Play A Role In Peripheral Nerve Regeneration
Author(s) -
Engber Tm,
Allendoerfer Kl,
Berg A,
Drake E,
Mahanthappa N,
Mozell R,
Pepicelli C,
Ranciato R,
Reilly Jo,
Sah D,
Wang S,
Galdes A.
Publication year - 2000
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2000abstracts-62.x
Subject(s) - sonic hedgehog , hedgehog signaling pathway , hedgehog , patched , endoneurium , indian hedgehog , biology , sciatic nerve , microbiology and biotechnology , anatomy , medicine , endocrinology , signal transduction
Hedgehog proteins are embryonic induction factors that play a role in the development of the central and peripheral nervous systems. The Hedgehog proteins and their signaling pathway continue to be expressed in the adult nervous system, where their role is not known. In adult peripheral nerve, Sonic Hedgehog (Shh) is expressed in a subset of motor neurons, Desert Hedgehog (Dhh) is expressed in Schwann cells, and the Hedgehog receptor Patched (Ptc) and the Hedgehog‐responsive transcription factor Gli are expressed predominantly in perineurial cells. We have used the mouse sciatic nerve crush model to assess whether the Hedgehog pathway plays a role in nerve regeneration. The sciatic nerve was crushed in adult, male CD‐1 mice, and the expression of Dhh, Ptc‐1, Ptc‐2 and Gli‐1 was examined 1, 3, 7 and 13 days later. The ability of exogenous and endogenous Hedgehog proteins to influence functional recovery after nerve crush was assessed by measuring toe spread and ability to grip with the hindpaws. Little change in expression was seen 1 or 3 days after nerve crush. At 7 days and, to a greater extent, 13 days, there was a pronounced increase in expression of Dhh in Schwann cells and Ptc‐1 in perineurial cells. Expression of Ptc‐2 and Gli‐1 increased not only in the perineurial layer, but also in the endoneurium. Treatment with a Shh‐Ig fusion protein (1 mg/kg s.c. every other day) improved recovery of both toe spread and ability to grip. Conversely, treatment with an anti‐Hedgehog neutralizing antibody (10 mg/kg s.c. every other day) slowed functional recovery, while an isotype control antibody had no effect. These findings suggest that endogenous Hedgehog proteins play a role in promoting regeneration following nerve injury and that administration of exogenous Hedgehog proteins can further accelerate recovery of injured peripheral nerves. Therefore, Hedgehog proteins may be useful in the treatment of nerve injury and peripheral neuropathies.