Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain.
Studies have indicated that oligodendrocytes in the spinal cord originate from a ventral progenitor domain defined by expression of the oligodendrocyte-determining bHLH proteins Olig1 and Olig2. Here, we provide evidence that progenitors in the dorsal spinal cord and hindbrain also produce oligodendrocytes and that the specification of these cells may result from a dorsal evasion of BMP signaling over time. Moreover, we show that the generation of ventral oligodendrocytes in the spinal cord depends on Nkx6.1 and Nkx6.2 function, while these homeodomain proteins in the anterior hindbrain instead suppress oligodendrocyte specification. The opposing roles for Nkx6 proteins in the spinal cord and hindbrain, in turn, appear to reflect that oligodendrocytes are produced by distinct ventral progenitor domains at these axial levels. Based on these findings, we propose that oligodendrocytes derive from several distinct positional origins and that the activation of Olig1/2 at different positions is controlled by distinct genetic programs.
Vallstedt
Anna
A
Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden.
Klos
Joanna M
JM
Ericson
Johan
J
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D051763:PAX7 Transcription Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D051763:PAX7 Transcription Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C491328:Nkx6-1 protein, mouse; C436827:Nkx6.2 protein, vertebrate; C494786:Olig1 protein, mouse; C512773:Olig2 protein, mouse; C497322:Pax7 protein, mouse