title: Betacellulin regulates schwann cell proliferation and myelin formation in the injured mouse peripheral nerve.
abstract: When a nerve fiber is cut or crushed, the axon segment that is separated from the soma degenerates distal from the injury in a process termed Wallerian degeneration (WD). C57BL/6OlaHsd-WldS(WldS) mutant mice exhibit significant delays in WD. This results in considerably delayed Schwann cell and macrophage responses and thus in impaired nerve regenerations. In our previous work, thousands of genes were screened by DNA microarrays and over 700 transcripts were found to be differentially expressed in the injured sciatic nerve of WldScompared with wild-type (WT) mice. One of these transcripts, betacellulin (Btc), was selected for further analysis since it has yet to be characterized in the nervous system, despite being known as a ligand of the ErbB receptor family. We show that Btc mRNA is strongly upregulated in immature and dedifferentiated Sox2+Schwann cells located in the sciatic nerve distal stump of WT mice, but not WldSmutants. Transgenic mice ubiquitously overexpressing Btc (Tg-Btc) have increased numbers of Schmidt-Lantermann incisures compared with WT mice, as revealed by Coherent anti-Stokes Raman scattering (CARS). Tg-Btc mice also have faster nerve conduction velocity. Finally, we found that deficiency in Btc reduces the proliferation of myelinating Schwann cells after sciatic nerve injury, while Btc overexpression induces Schwann cell proliferation and improves recovery of locomotor function. Taken together, these results suggest a novel regulatory role of Btc in axon-Schwann cell interactions involved in myelin formation and nerve repair. GLIA 2017 GLIA 2017;65:657-669.
authors.affiliation: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec-CHUL et Département de médecine moléculaire, Faculté de médecine, Université Laval, Québec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vallières
authors.affiliation: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec-CHUL et Département de médecine moléculaire, Faculté de médecine, Université Laval, Québec, Canada.
authors.forename: Benoit
authors.initials: B
authors.lastname: Barrette
authors.affiliation: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec-CHUL et Département de médecine moléculaire, Faculté de médecine, Université Laval, Québec, Canada.
authors.forename: Linda Xiang
authors.initials: LX
authors.lastname: Wang
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec (CRIUSMQ) et Département de physique, génie physique et optique, Faculté des sciences et de génie, Université Laval, Québec, Canada.|Centre d'optique, photonique et laser (COPL), Université Laval, Québec, Canada.
authors.forename: Erik
authors.initials: E
authors.lastname: Bélanger
authors.affiliation: Centre de recherche du CHU de Québec-CHUL et Département de psychiatrie et de neurosciences de l'Université Laval, Faculté de Médecine, Université Laval, Québec, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Thiry
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany.
authors.forename: Marlon R
authors.initials: MR
authors.lastname: Schneider
authors.affiliation: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec-CHUL et Département de médecine moléculaire, Faculté de médecine, Université Laval, Québec, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Filali
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec (CRIUSMQ) et Département de physique, génie physique et optique, Faculté des sciences et de génie, Université Laval, Québec, Canada.|Centre d'optique, photonique et laser (COPL), Université Laval, Québec, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Côté
authors.affiliation: Centre de recherche du CHU de Québec-CHUL et Département de psychiatrie et de neurosciences de l'Université Laval, Faculté de Médecine, Université Laval, Québec, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bretzner
authors.affiliation: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec-CHUL et Département de médecine moléculaire, Faculté de médecine, Université Laval, Québec, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Lacroix
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D066259:Betacellulin / Q000235:genetics / Q000378:metabolism; D018845:CD11 Antigens / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D004195:Disease Models, Animal; D051767:Early Growth Response Protein 2 / Q000378:metabolism; D004558:Electric Stimulation; D005786:Gene Expression Regulation / Q000235:genetics*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009186:Myelin Sheath / Q000502:physiology*; D009416:Nerve Regeneration / Q000235:genetics; D009431:Neural Conduction / Q000235:genetics / Q000502:physiology; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D066259:Betacellulin; D018845:CD11 Antigens; D051767:Early Growth Response Protein 2; D055748:SOXB1 Transcription Factors; C587852:Btc protein, mouse; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C527783:Sox2 protein, mouse
keywords: ErbB receptor; Schmidt-Lantermann incisure; Schwann cells; Wallerian degeneration; demyelination; node of Ranvier; peripheral nervous system; remyelination; sciatic nerve injury