title: In vivo analysis of oligodendrocyte lineage development in postnatal FGF2 null mice.
abstract: Analysis of fibroblast growth factor 2 null (FGF2-/-) and wild-type (FGF2+/+) mice was used to interpret the potential in vivo role of endogenous FGF2 on oligodendrocyte lineage cell (OLC) responses during oligodendrogenesis and myelination. In wild-type mouse spinal cord, FGF2 levels increased approximately threefold between the first and second postnatal weeks, a period corresponding with the peak of oligodendrogenesis. Absence of this developmental FGF2 elevation in FGF2-/- mice eliminated the transient overproduction of oligodendrocytes that is known to occur at the peak of oligodendrogenesis in wild-type mice. Absence of FGF2 did not affect oligodendrocyte progenitor (OP) density or proliferation, based on BrdU incorporation, and also did not alter survival, based on TUNEL analysis. To examine OLC differentiation in vivo, retrovirus encoding-enhanced green fluorescent protein (GFP) was injected into the spinal cord to heritably label endogenous cycling cells in the white matter at postnatal day 7 and then identify the generated cells at postnatal day 28. Phenotypes of cells expressing GFP were identified by morphology and immunolabeling, using CC1 for oligodendrocytes and NG2 combined with platelet-derived growth factor alpha receptor for OPs. Within the population of GFP-labeled cells, the proportion of oligodendrocytes was higher in FGF2-/- mice, indicating that endogenous FGF2 inhibited OLC differentiation in wild-type mice. Furthermore, in FGF2-/- mice fewer cells appeared to be generated from an initial retrovirus-labeled cell, consistent with more frequent differentiation into post-mitotic oligodendrocytes. This in vivo analysis demonstrates that the predominant role of endogenous FGF2 on OLCs in development is inhibition of differentiation.
authors.affiliation: Program in Molecular and Cell Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Murtie
authors.forename: Yong-Xing
authors.initials: YX
authors.lastname: Zhou
authors.forename: Tuan Q
authors.initials: TQ
authors.lastname: Le
authors.forename: Regina C
authors.initials: RC
authors.lastname: Armstrong
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D000071183:Autophagy-Related Proteins; D015415:Biomarkers; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D000071183:Autophagy-Related Proteins; D015415:Biomarkers; D001973:Bromodeoxyuridine; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011509:Proteoglycans; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor; D000099216:Chondroitin Sulfate Proteoglycan 4; C428743:Rb1cc1 protein, mouse; C496353:FGFR2 protein, human; C496354:Fgfr2 protein, mouse