| RRC ID |
88270
|
| Author |
Clements MP, Byrne E, Camarillo Guerrero LF, Cattin AL, Zakka L, Ashraf A, Burden JJ, Khadayate S, Lloyd AC, Marguerat S, Parrinello S.
|
| Title |
The Wound Microenvironment Reprograms Schwann Cells to Invasive Mesenchymal-like Cells to Drive Peripheral Nerve Regeneration.
|
| Journal |
Neuron
|
| Abstract |
Schwann cell dedifferentiation from a myelinating to a progenitor-like cell underlies the remarkable ability of peripheral nerves to regenerate following injury. However, the molecular identity of the differentiated and dedifferentiated states in vivo has been elusive. Here, we profiled Schwann cells acutely purified from intact nerves and from the wound and distal regions of severed nerves. Our analysis reveals novel facets of the dedifferentiation response, including acquisition of mesenchymal traits and a Myc module. Furthermore, wound and distal dedifferentiated Schwann cells constitute different populations, with wound cells displaying increased mesenchymal character induced by localized TGFβ signaling. TGFβ promotes invasion and crosstalks with Eph signaling via N-cadherin to drive collective migration of the Schwann cells across the wound. Consistently, Tgfbr2 deletion in Schwann cells resulted in misdirected and delayed reinnervation. Thus, the wound microenvironment is a key determinant of Schwann cell identity, and it promotes nerve repair through integration of multiple concerted signals. VIDEO ABSTRACT.
|
| Volume |
96(1)
|
| Pages |
98-114.e7
|
| Published |
2017-9-27
|
| DOI |
10.1016/j.neuron.2017.09.008
|
| PII |
S0896-6273(17)30843-7
|
| PMID |
28957681
|
| PMC |
PMC5626803
|
| MeSH |
Animals
Cadherins / physiology
Cell Differentiation*
Cell Movement / physiology
Cells, Cultured
Cellular Microenvironment / physiology*
Female
Male
Mesenchymal Stem Cells / cytology*
Mesenchymal Stem Cells / physiology*
Mice
Mice, Transgenic
Nerve Regeneration / physiology*
Peripheral Nerve Injuries / pathology
Peripheral Nerve Injuries / physiopathology*
Primary Cell Culture
Rats
Rats, Transgenic
Receptors, Eph Family / physiology
Schwann Cells / cytology*
Schwann Cells / physiology*
Sciatic Nerve / injuries
Sciatic Nerve / physiology
Transforming Growth Factor beta / genetics
Transforming Growth Factor beta / physiology
|
| Resource |
| Mice |
RBRC01459 |
