Scientific Understanding of Consciousness
Oligodendrocyte Precursors Migrate along Vasculature in Developing CNS
Science 22 Jan 2016: Vol. 351, Issue 6271, pp. 379-384
Oligodendrocyte precursors migrate along vasculature in the developing nervous system
Hui-Hsin Tsai1, et.al.
Department of Pediatrics, University of California at San Francisco (UCSF), San Francisco, CA 94158, USA.
Departments of Pharmacology and Neuroscience, University of California at San Diego (UCSD), San Diego, CA 92093, USA.
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Division of Hematology, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Department of Urology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Howard Hughes Medical Institute (HHMI), Chevy Chase, MD 20815, USA.
Duke University School of Medicine, Durham, NC 27710, USA.
Department of Neurology, UCSF, San Francisco, CA 94158, USA.
Division of Neonatology, UCSF, San Francisco, CA 94158, USA.
Newborn Brain Research Institute, UCSF, San Francisco, CA 94158, USA.
Oligodendrocytes myelinate axons in the central nervous system and develop from oligodendrocyte precursor cells (OPCs) that must first migrate extensively during brain and spinal cord development. We show that OPCs require the vasculature as a physical substrate for migration. We observed that OPCs of the embryonic mouse brain and spinal cord, as well as the human cortex, emerge from progenitor domains and associate with the abluminal endothelial surface of nearby blood vessels. Migrating OPCs crawl along and jump between vessels. OPC migration in vivo was disrupted in mice with defective vascular architecture but was normal in mice lacking pericytes. Thus, physical interactions with the vascular endothelium are required for OPC migration. We identify Wnt-Cxcr4 (chemokine receptor 4) signaling in regulation of OPC-endothelial interactions and propose that this signaling coordinates OPC migration with differentiation.
Oligodendrocytes, the myelinating cells of the central nervous system (CNS), support rapid saltatory nerve conduction and maintain axon integrity through metabolic coupling. Oligodendrocyte precursor cells (OPCs) arise from the ventricular zone in the embryonic brain and spinal cord, in domains defined through pattern formation. From these domains, OPCs migrate widely through the CNS to achieve uniform distribution.
The CNS is built by cells migrating away from their places of origin to construct mature neural tissue. Neuroblasts disperse in radial and tangential patterns following substrates such as radial glial cells, corticofugal fibers, or Bergmann glia. Postnatal neuronal migration is more limited. In the rostral migratory stream, neuroblasts crawl over one another and along blood vessels to get from the subventricular zone to the olfactory bulb. Astrocytes seem to migrate only radially during development, following radial glia without secondary tangential migration. Thus, astrocytes occupy restricted spatial domains in adulthood related to their embryonic site of origin.
Oligodendrocyte precursor cells, which migrate more extensively than neurons and other glia, must also recognize their path and migrate through often-compact developing tissue before interactions with their targets halt their migration. OPCs also maintain this capacity in response to demyelination in the adult CNS. OPC motility is regulated by cell-intrinsic mechanisms, polarity, and extracellular cues. Various substrates have been proposed as putative candidates for OPC migration. Here we show that OPCs migrate along the vasculature through the developing CNS and that Wnt signaling regulates these OPC-endothelial interactions.
The mechanisms directing OPC migration during development are likely to be similar, if not identical, to those of the injured or diseased nervous system. OPC migration into demyelinated areas is critical in human diseases such as multiple sclerosis and also in hypoxic injury of the newborn brain. It will be important to establish the contribution of this mode of migration for OPC distribution into areas of injury and to uncover how dysfunction may contribute to disease progression in these debilitating human conditions.
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