Cthrc1 is a negative regulator of myelination in Schwann cells

Glia. 2012 Mar;60(3):393-403. doi: 10.1002/glia.22273.

Abstract

The analysis of the molecular mechanisms involved in the initial interaction between neurons and Schwann cells is a key issue in understanding the myelination process. We recently identified Cthrc1 (Collagen triple helix repeat containing 1) as a gene upregulated in Schwann cells upon interaction with the axon. Cthrc1 encodes a secreted protein previously shown to be involved in migration and proliferation in different cell types. We performed a functional analysis of Cthrc1 in Schwann cells by loss-of- and gain-of-function approaches using RNA interference knockdown in cell culture and a transgenic mouse line that overexpresses the gene. This work establishes that Cthrc1 enhances Schwann cell proliferation but prevents myelination. In particular, time-course analysis of myelin formation intransgenic animals reveals that overexpression of Cthrc1 in Schwann cells leads to a delay in myelin formation with cells maintaining a proliferative state. Our data, therefore, demonstrate that Cthrc1 plays a negative regulatory role, fine-tuning the onset of peripheral myelination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Early Growth Response Protein 2 / genetics
  • Embryo, Mammalian
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Ganglia, Spinal / cytology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron
  • Myelin Basic Protein / metabolism
  • RNA, Small Interfering / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Schwann Cells / metabolism*
  • Schwann Cells / ultrastructure
  • Time Factors
  • Transfection

Substances

  • Cthrc1 protein, mouse
  • Early Growth Response Protein 2
  • Egr2 protein, mouse
  • Extracellular Matrix Proteins
  • Myelin Basic Protein
  • RNA, Small Interfering
  • Green Fluorescent Proteins
  • Bromodeoxyuridine