title: Cthrc1 is a negative regulator of myelination in Schwann cells.
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.
authors.affiliation: Ecole Normale Supérieure, IBENS, Developmental Biology Section, 75230 Paris cedex 05, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Apra
authors.forename: Laurence
authors.initials: L
authors.lastname: Richard
authors.forename: Fanny
authors.initials: F
authors.lastname: Coulpier
authors.forename: Corinne
authors.initials: C
authors.lastname: Blugeon
authors.forename: Pascale
authors.initials: P
authors.lastname: Gilardi-Hebenstreit
authors.forename: Jean-michel
authors.initials: JM
authors.lastname: Vallat
authors.forename: Volkhard
authors.initials: V
authors.lastname: Lindner
authors.forename: Patrick
authors.initials: P
authors.lastname: Charnay
authors.forename: Laurence
authors.initials: L
authors.lastname: Decker
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D051767:Early Growth Response Protein 2 / Q000235:genetics; D004622:Embryo, Mammalian; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D004676:Myelin Basic Protein / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors; D014162:Transfection
chemical_list: C530500:Cthrc1 protein, mouse; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D016326:Extracellular Matrix Proteins; D004676:Myelin Basic Protein; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine