Intrinsic and extrinsic inhibition of oligodendrocyte development by rat retina.
Cell patterning in the vertebrate CNS reflects the combination of localized cell induction, migration and differentiation. A striking example of patterning is the myelination of visual system. In many species, retinal ganglion cell axons are myelinated in the optic nerve but are unmyelinated in the retina. Here, we confirm that rat and mouse retina lack oligodendrocytes and their precursors and identify multiple mechanisms that might contribute to their absence. Soluble cues from embryonic retina inhibit the induction of oligodendrocytes from neural stem cells and their differentiation from optic nerve precursors. This inhibition is mediated by retinal-derived BMPs. During development BMPs are expressed in the retina and addition of the BMP antagonist Noggin reversed retinal inhibition of oligodendrocyte development. The lack of retinal oligodendrocytes does not simply reflect expression of BMPs, since no oligodendrocytes or their precursors developed when embryonic retinal cells were grown in the presence of Noggin and/or inductive cues such as Shh and IGF-1. Similarly, injection of Noggin into the postnatal rat eye failed to induce oligodendrocyte differentiation. These data combined with the proposed inhibition of OPC migration by molecules selectively expressed at the nerve retina junction suggest that multiple mechanisms combine to suppress retinal myelination during development.
Gao
Limin
L
Department of Neurosciences, Case School of Medicine, Cleveland, OH 44106, USA.
Macklin
Wendy
W
Gerson
James
J
Miller
Robert H
RH
D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D051381:Rats; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D007334:Insulin-Like Growth Factor I; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; C525810:Bmp4 protein, mouse; C525811:Bmp4 protein, rat; C525821:Bmp7 protein, rat; C485184:enhanced green fluorescent protein