Patterning of spinal cord oligodendrocyte development by dorsally derived BMP4.
Oligodendrocyte precursors (OPCs) initially arise in the motor neuron domain of the ventral ventricular zone of the developing spinal cord. After dispersal throughout gray and white matter, OPCs differentiate in a characteristic ventral to dorsal sequence. The spatial localization of OPC induction is in part a result of both positive local sonic hedgehog signaling and dorsally derived inhibitory cues. One component of dorsal inhibitory signals seems to be members of the transforming growth factor beta (TGFbeta) superfamily such as the bone morphogenetic proteins (BMPs). We show that during the initial appearance and subsequent maturation of OPCs, BMP4 was expressed specifically in the dorsal midline and its expression was correlated spatially and temporally with phospho-Smad 1+, BMP4-responsive cells. Implantation of sonic hedgehog (Shh)-coated beads adjacent to dorsal spinal cord in Xenopus embryos induced ectopic dorsal OPCs whereas BMP4-coated beads inhibited OPC appearance. More importantly, blocking endogenous dorsal BMP4 with anti-BMP4-coated beads locally induced ectopic OPCs. Similar results were obtained using soluble ligands on slice preparations of rodent spinal cord in vitro. In dissociated cell cultures of embryonic rat spinal cord, Shh and BMP4 had antagonistic effects on OPC development and the sensitivity of oligodendrocyte lineage cells to BMP4 increased with maturation. These data suggest that BMP4 contributes to the pattern of spinal cord oligodendrogenesis by regulating both induction and maturation of spinal cord OPCs.
Miller
Robert H
RH
Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA. rhm3@po.cwru.edu
Dinsio
Kyl
K
Wang
Rae
R
Geertman
Robert
R
Maier
Charles E
CE
Hall
Alison K
AK
D000818:Animals; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000502:physiology; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D009836:Oligodendroglia / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D013116:Spinal Cord / Q000166:cytology*; D013234:Stem Cells / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014981:Xenopus; D029867:Xenopus Proteins
C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D015534:Trans-Activators; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus