title: Temporal Analysis of Gene Expression in the Murine Schwann Cell Lineage and the Acutely Injured Postnatal Nerve.
abstract: Schwann cells (SCs) arise from neural crest cells (NCCs) that first give rise to SC precursors (SCPs), followed by immature SCs, pro-myelinating SCs, and finally, non-myelinating or myelinating SCs. After nerve injury, mature SCs 'de-differentiate', downregulating their myelination program while transiently re-activating early glial lineage genes. To better understand molecular parallels between developing and de-differentiated SCs, we characterized the expression profiles of a panel of 12 transcription factors from the onset of NCC migration through postnatal stages, as well as after acute nerve injury. Using Sox10 as a pan-glial marker in co-expression studies, the earliest transcription factors expressed in E9.0 Sox10+ NCCs were Sox9, Pax3, AP2α and Nfatc4. E10.5 Sox10+ NCCs coalescing in the dorsal root ganglia differed slightly, expressing Sox9, Pax3, AP2α and Etv5. E12.5 SCPs continued to express Sox10, Sox9, AP2α and Pax3, as well as initiating Sox2 and Egr1 expression. E14.5 immature SCs were similar to SCPs, except that they lost Pax3 expression. By E18.5, AP2α, Sox2 and Egr1 expression was turned off in the nerve, while Jun, Oct6 and Yy1 expression was initiated in pro-myelinating Sox9+/Sox10+ SCs. Early postnatal and adult SCs continued to express Sox9, Jun, Oct6 and Yy1 and initiated Nfatc4 and Egr2 expression. Notably, at all stages, expression of each marker was observed only in a subset of Sox10+ SCs, highlighting the heterogeneity of the SC pool. Following acute nerve injury, Egr1, Jun, Oct6, and Sox2 expression was upregulated, Egr2 expression was downregulated, while Sox9, Yy1, and Nfatc4 expression was maintained at similar frequencies. Notably, de-differentiated SCs in the injured nerve did not display a transcription factor profile corresponding to a specific stage in the SC lineage. Taken together, we demonstrate that uninjured and injured SCs are heterogeneous and distinct from one another, and de-differentiation recapitulates transcriptional aspects of several different embryonic stages.
authors.affiliation: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Anjali
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Morgan G
authors.initials: MG
authors.lastname: Stykel
authors.affiliation: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Touahri
authors.affiliation: Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Department of Clinical Neurosciences, Cumming School of Medicine, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Jo Anne
authors.initials: JA
authors.lastname: Stratton
authors.affiliation: Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Jeff
authors.initials: J
authors.lastname: Biernaskie
authors.affiliation: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Carol
authors.initials: C
authors.lastname: Schuurmans
mesh_terms: D000208:Acute Disease; D000818:Animals; D054337:Cell Dedifferentiation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000235:genetics* / Q000473:pathology*; D055747:SOX Transcription Factors / Q000235:genetics; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome
chemical_list: D005819:Genetic Markers; D055747:SOX Transcription Factors; D014157:Transcription Factors