Oligodendrocyte precursors migrate along vasculature in the developing nervous system

Neuronal migrations follow vascular pathways In the developing brain, various types of cells migrate from their birthplaces to their workplaces. Oligodendrocyte precursors, which develop to form the insulating sheaths that make signal transmission along an axon faster, travel farther than many. Tsai et al. now show just how the oligodendrocyte precursor cells find their way (see the Perspective by Dejana and Beltsholtz). The progenitor cells follow along the endothelial cells of the vasculature. Disrupting endothelial cells interfered with oligodendrocyte migration, leaving some sections of the brain deficient in insulators. Science, this issue p. 379; see also p. 341 Cells that migrate far and wide through the developing brain follow blood vessels to find their way. [Also see Perspective by Dejana and Beltsholtz] 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.

[1]  J. Nathans,et al.  Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis , 2015, eLife.

[2]  S. Seaman,et al.  GPR124 functions as a WNT7-specific coactivator of canonical β-catenin signaling. , 2015, Cell reports.

[3]  D. Rowitch,et al.  Oligodendrocyte-Encoded HIF Function Couples Postnatal Myelination and White Matter Angiogenesis , 2014, Cell.

[4]  E. Huang,et al.  Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer , 2014, Nature Neuroscience.

[5]  J. Trotter,et al.  NG2 Regulates Directional Migration of Oligodendrocyte Precursor Cells via Rho GTPases and Polarity Complex Proteins , 2013, The Journal of Neuroscience.

[6]  Y. Choe,et al.  Wnt Signaling Regulates Intermediate Precursor Production in the Postnatal Dentate Gyrus by Regulating Cxcr4 Expression , 2012, Developmental Neuroscience.

[7]  A. Álvarez-Buylla,et al.  Regional Astrocyte Allocation Regulates CNS Synaptogenesis and Repair , 2012, Science.

[8]  Pierre J. Magistretti,et al.  Oligodendroglia metabolically support axons and contribute to neurodegeneration , 2012, Nature.

[9]  Jens Frahm,et al.  Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity , 2012, Nature.

[10]  Zhuoxun Chen,et al.  Perivascular instruction of cell genesis and fate in the adult brain , 2011, Nature Neuroscience.

[11]  S. Miller,et al.  The role of CXCR4 signaling in the migration of transplanted oligodendrocyte progenitors into the cerebral white matter , 2011, Neurobiology of Disease.

[12]  E. Huang,et al.  Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination , 2011, Nature Neuroscience.

[13]  B. Barres,et al.  Pericytes are required for blood–brain barrier integrity during embryogenesis , 2010, Nature.

[14]  Hua Su,et al.  Essential Regulation of CNS Angiogenesis by the Orphan G Protein–Coupled Receptor GPR124 , 2010, Science.

[15]  B. Roysam,et al.  Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling. , 2010, Cell stem cell.

[16]  P. Devilee,et al.  A new conditional Apc-mutant mouse model for colorectal cancer. , 2010, Carcinogenesis.

[17]  D. Rowitch,et al.  Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. , 2009, Genes & development.

[18]  A. Parent,et al.  Vasculature Guides Migrating Neuronal Precursors in the Adult Mammalian Forebrain via Brain-Derived Neurotrophic Factor Signaling , 2009, The Journal of Neuroscience.

[19]  Calvin J Kuo,et al.  Wnt/β-catenin signaling is required for CNS, but not non-CNS, angiogenesis , 2009, Proceedings of the National Academy of Sciences.

[20]  Andrew P. McMahon,et al.  Canonical Wnt Signaling Regulates Organ-Specific Assembly and Differentiation of CNS Vasculature , 2008, Science.

[21]  Robin J. M. Franklin,et al.  Remyelination in the CNS: from biology to therapy , 2008, Nature Reviews Neuroscience.

[22]  A. Tanoue,et al.  Cdk5 Phosphorylation of WAVE2 Regulates Oligodendrocyte Precursor Cell Migration through Nonreceptor Tyrosine Kinase Fyn , 2008, The Journal of Neuroscience.

[23]  Tao Sun,et al.  Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. , 2008, Cancer cell.

[24]  M. Wegner,et al.  Sox9 and Sox10 influence survival and migration of oligodendrocyte precursors in the spinal cord by regulating PDGF receptor α expression , 2008, Development.

[25]  Palma Iannarelli,et al.  Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage , 2006, Nature Neuroscience.

[26]  P. Lau,et al.  A role for CXCR4 signaling in survival and migration of neural and oligodendrocyte precursors , 2005, Glia.

[27]  D. Chapman,et al.  The neural tube patterns vessels developmentally using the VEGF signaling pathway , 2004, Development.

[28]  Philippe Soriano,et al.  Additive Effects of PDGF Receptor β Signaling Pathways in Vascular Smooth Muscle Cell Development , 2003, PLoS biology.

[29]  M. Tessier-Lavigne,et al.  Netrin 1 mediates spinal cord oligodendrocyte precursor dispersal , 2003, Development.

[30]  R. Ransohoff,et al.  The Chemokine Receptor CXCR2 Controls Positioning of Oligodendrocyte Precursors in Developing Spinal Cord by Arresting Their Migration , 2002, Cell.

[31]  Tao Sun,et al.  Common Developmental Requirement for Olig Function Indicates a Motor Neuron/Oligodendrocyte Connection , 2002, Cell.

[32]  D. Rowitch,et al.  Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon. , 2001, Development.

[33]  C. ffrench-Constant,et al.  Knockout mice reveal a contribution of the extracellular matrix molecule tenascin-C to neural precursor proliferation and migration. , 2001, Development.

[34]  Jaime Grutzendler,et al.  Two modes of radial migration in early development of the cerebral cortex , 2001, Nature Neuroscience.

[35]  Masahiko Kuroda,et al.  Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development , 1998, Nature.

[36]  A. Gansmuller,et al.  Cell‐cell interactions during the migration of myelin‐forming cells transplanted in the demyelinated spinal cord , 1996, Glia.

[37]  P. Rakić,et al.  Dynamics of granule cell migration: a confocal microscopic study in acute cerebellar slice preparations , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[38]  C. Lois,et al.  Long-distance neuronal migration in the adult mammalian brain. , 1994, Science.

[39]  S. Mcconnell,et al.  Diverse migratory pathways in the developing cerebral cortex. , 1992, Science.

[40]  P. Rakić,et al.  Neuronal migration, with special reference to developing human brain: a review. , 1973, Brain research.