NG2 glia are required for vessel network formation during embryonic development

The NG2+ glia, also known as polydendrocytes or oligodendrocyte precursor cells, represent a new entity among glial cell populations in the central nervous system. However, the complete repertoire of their roles is not yet identified. The embryonic NG2+ glia originate from the Nkx2.1+ progenitors of the ventral telencephalon. Our analysis unravels that, beginning from E12.5 until E16.5, the NG2+ glia populate the entire dorsal telencephalon. Interestingly, their appearance temporally coincides with the establishment of blood vessel network in the embryonic brain. NG2+ glia are closely apposed to developing cerebral vessels by being either positioned at the sprouting tip cells or tethered along the vessel walls. Absence of NG2+ glia drastically affects the vascular development leading to severe reduction of ramifications and connections by E18.5. By revealing a novel and fundamental role for NG2+ glia, our study brings new perspectives to mechanisms underlying proper vessels network formation in embryonic brains. DOI: http://dx.doi.org/10.7554/eLife.09102.001

• Publication year

  2015

• Venue

  eLife

• Publication date

  2015-12-10

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.7554/eLife.09102PMID 26651999PMCID 4764555
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Nkx2.1-derived astrocytes and neurons together with Slit2 are indispensable for anterior commissure formation

  2015cited by this paper
• Decision making during interneuron migration in the developing cerebral cortex.

  2014cited by this paper
• Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis.

  2014cited by this paper
• NG2 Regulates Directional Migration of Oligodendrocyte Precursor Cells via Rho GTPases and Polarity Complex Proteins

  2013cited by this paper
• Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain

  2013influential reference
• Astrocyte-Derived Sonic Hedgehog Contributes to Angiogenesis in Brain Microvascular Endothelial Cells via RhoA/ROCK Pathway After Oxygen–Glucose Deprivation

  2013cited by this paper
• NG2 Cells in White Matter But Not Gray Matter Proliferate in Response to PDGF

  2013cited by this paper
• Macrophages and angiogenesis: a role for Wnt signaling

  2012influential reference
• Self-renewal does not predict tumor growth potential in mouse models of high-grade glioma.

  2012cited by this paper
• Properties and Fate of Oligodendrocyte Progenitor Cells in the Corpus Callosum, Motor Cortex, and Piriform Cortex of the Mouse

  2012cited by this paper
• Polydendrocytes Display Large Lineage Plasticity following Focal Cerebral Ischemia

  2012cited by this paper
• The interplay between macrophages and angiogenesis in development, tissue injury and regeneration.

  2011influential reference
• Asymmetry-defective oligodendrocyte progenitors are glioma precursors.

  2011cited by this paper
• Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma

  2011cited by this paper
• Notch1 controls macrophage recruitment and Notch signaling is activated at sites of endothelial cell anastomosis during retinal angiogenesis in mice.

  2011influential reference
• Excitability and Synaptic Communication within the Oligodendrocyte Lineage

  2010cited by this paper
• Pericytes are required for blood–brain barrier integrity during embryogenesis

  2010cited by this paper
• Axon guidance molecules in vascular patterning.

  2010cited by this paper
• Pericytes regulate the blood–brain barrier

  2010cited by this paper
• Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction.

  2010influential reference
• Non-stem cell origin for oligodendroglioma.

  2010cited by this paper
• Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma

  2009cited by this paper
• Trophic macrophages in development and disease

  2009influential reference
• Guidance of Vascular Development: Lessons From the Nervous System

  2009influential reference
• Cell migration in the normal and pathological postnatal mammalian brain.

  2009cited by this paper
• Transcriptional regulation of tangential neuronal migration in the developing forebrain.

  2009cited by this paper
• Brain angiogenesis in developmental and pathological processes: therapeutic aspects of vascular endothelial growth factor

  2009influential reference
• Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity

  2009influential reference
• Fate mapping Nkx2.1‐lineage cells in the mouse telencephalon

  2008cited by this paper
• NG2 cells generate oligodendrocytes and gray matter astrocytes in the spinal cord.

  2008influential reference
• Canonical Wnt Signaling Regulates Organ-Specific Assembly and Differentiation of CNS Vasculature

  2008cited by this paper
• Angiogenesis in the embryonic CNS

  2008influential reference
• Endogenous or exogenous oligodendrocytes for remyelination.

  2008cited by this paper
• A time and a place for nkx2-1 in interneuron specification and migration.

  2008cited by this paper
• NKX2.1 specifies cortical interneuron fate by activating Lhx6

  2008cited by this paper
• PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice

  2008influential reference
• Compartment-specific transcription factors orchestrate angiogenesis gradients in the embryonic brain

  2008cited by this paper
• A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function

  2008cited by this paper
• Initiation of Oligodendrocyte Progenitor Cell Migration by a PDGF-A Activated Extracellular Regulated Kinase (ERK) Signaling Pathway

  2008cited by this paper
• A role for the NG2 proteoglycan in glioma progression

  2008cited by this paper
• Faculty Opinions recommendation of Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis.

  2007cited by this paper
• Innate versus learned odour processing in the mouse olfactory bulb

  2007cited by this paper
• Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis

  2007cited by this paper
• NG2 cells generate both oligodendrocytes and gray matter astrocytes

  2007influential reference
• Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting

  2007cited by this paper
• Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis

  2007cited by this paper
• Polydendrocytes: NG2 Cells with Many Roles in Development and Repair of the CNS

  2007cited by this paper
• Vascular endothelial growth factor receptor 3 is involved in tumor angiogenesis and growth.

  2007influential reference
• An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis

  2007cited by this paper
• The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching

  2007cited by this paper
• Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth.

  2007cited by this paper
• Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis.

  2007cited by this paper
• Molecular regulation of angiogenesis and lymphangiogenesis

  2007influential reference
• An improved mouse line for Cre‐induced cell ablation due to diphtheria toxin A, expressed from the Rosa26 locus

  2006cited by this paper
• VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells.

  2006cited by this paper
• Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage

  2006cited by this paper
• Synaptic communication between neurons and NG2+ cells.

  2006influential reference
• Netrins Promote Developmental and Therapeutic Angiogenesis

  2006cited by this paper
• Notch signalling: a simple pathway becomes complex

  2006cited by this paper
• Semaphorin 3E and Plexin-D1 Control Vascular Pattern Independently of Neuropilins

  2005cited by this paper
• The role of pericytes in blood-vessel formation and maintenance.

  2005cited by this paper
• Common mechanisms of nerve and blood vessel wiring

  2005influential reference
• Neural guidance molecules regulate vascular remodeling and vessel navigation.

  2005cited by this paper
• The molecular orchestra of the migration of oligodendrocyte precursors during development.

  2005cited by this paper
• Endothelial cells and VEGF in vascular development

  2005cited by this paper
• NG2‐expressing cells as oligodendrocyte progenitors in the normal and demyelinated adult central nervous system

  2005cited by this paper
• Synantocytes: the fifth element

  2005influential reference
• Semaphorins command cells to move

  2005cited by this paper
• Cell‐autonomous notch signaling regulates endothelial cell branching and proliferation during vascular tubulogenesis

  2005cited by this paper
• Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors

  2005cited by this paper
• roundabout4 is essential for angiogenesis in vivo.

  2005cited by this paper
• Semaphorins in cancer.

  2005cited by this paper
• PlexinD1 and semaphorin signaling are required in endothelial cells for cardiovascular development.

  2004cited by this paper
• Origins of Cortical Interneuron Subtypes

  2004cited by this paper
• Postnatal Neurogenesis and Gliogenesis in the Olfactory Bulb from NG2-Expressing Progenitors of the Subventricular Zone

  2004cited by this paper
• The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system

  2004cited by this paper
• Semaphorin-plexin signaling guides patterning of the developing vasculature.

  2004cited by this paper
• Neuropilin‐1 is required for endothelial tip cell guidance in the developing central nervous system

  2004cited by this paper
• Robo4 is a vascular-specific receptor that inhibits endothelial migration.

  2003cited by this paper
• The biology of VEGF and its receptors

  2003influential reference
• Molecular regulation of vessel maturation

  2003cited by this paper
• Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67‐GFP knock‐in mouse

  2003cited by this paper
• The role of neuropilin in vascular and tumor biology.

  2002cited by this paper
• The neuropilins: multifunctional semaphorin and VEGF receptors that modulate axon guidance and angiogenesis.

  2002cited by this paper
• Development of pharyngeal arch arteries in early mouse embryo

  2002influential reference
• Identity, distribution, and development of polydendrocytes: NG2-expressing glial cells

  2002cited by this paper
• Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis.

  2002cited by this paper
• Guidance of glial precursor cell migration by secreted cues in the developing optic nerve.

  2001cited by this paper
• Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus

  2001cited by this paper
• JCB Article

  2001cited by this paper
• NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis

  2001cited by this paper
• Guidance of glial precursor cell migration by secreted cues in the developing optic nerve

  2001influential reference
• Telencephalic cells take a tangent: non-radial migration in the mammalian forebrain

  2001cited by this paper
• Distinct cortical migrations from the medial and lateral ganglionic eminences.

  2001cited by this paper
• Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain.

  2001influential reference
• A long, remarkable journey: Tangential migration in the telencephalon

  2001cited by this paper
• Vasculogenesis and Angiogenesis as Mechanisms of Vascular Network Formation, Growth and Remodeling

  2000cited by this paper
• [Mechanisms of angiogenesis in the brain].

  2000cited by this paper
• Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum.

  1999cited by this paper
• Mechanisms of angiogenesis in the brain.

  1999cited by this paper

• The HCF-1:OGT axis regulates neuronal proliferation and differentiation.

  2026cites this paper
• Characterizing hypoxia-orchestrated post-stroke changes in oligodendrocyte precursor cells for optimized cell therapy

  2025cites this paper
• Progenitor Timing Shapes NG2-Glia Fate and Oligodendrocyte Differentiation

  2025cites this paper
• The Role of Oligodendrocytes in Alzheimer’s Disease Pathogenesis and Therapy

  2025cites this paper
• Dynamic Interaction of Oligodendrocyte Precursor Cells with Other Cell Types in the Central Nervous System.

  2025cites this paper
• Pericytes in the Optic Nerve Head.

  2025cites this paper
• The Many Lives of an Oligodendrocyte Precursor Cell.

  2025cites this paper
• Pericytes as the Orchestrators of Vasculature and Adipogenesis

  2024cites this paper
• The role of oligodendrocyte progenitor cells in the spatiotemporal vascularization of the human and mouse neocortex

  2024cites this paper
• A molecularly defined subpopulation of oligodendrocyte precursor cells controls the generation of myelinating oligodendrocytes during postnatal development

  2024cites this paper
• Preserving and enhancing mitochondrial function after stroke to protect and repair the neurovascular unit: novel opportunities for nanoparticle-based drug delivery

  2023cites this paper
• Oligodendrocyte precursor cells: the multitaskers in the brain

  2023cites this paper
• The NG2-glia is a potential target to maintain the integrity of neurovascular unit after acute ischemic stroke.

  2023cites this paper
• Shaping the brain vasculature in development and disease in the single-cell era

  2023cites this paper
• Astrocyte ensheathment of calyx‐forming axons of the auditory brainstem precedes accelerated expression of myelin genes and myelination by oligodendrocytes

  2023cites this paper
• A molecularly-defined non-redundant subpopulation of OPCs controls the generation of myelinating oligodendrocytes during postnatal development

  2023cites this paper
• Oligodendrocyte precursors guide interneuron migration by unidirectional contact repulsion

  2022cites this paper
• Roles of NG2 Glia in Cerebral Small Vessel Disease

  2022cites this paper
• Step by step: cells with multiple functions in cortical circuit assembly

  2022cites this paper
• Reciprocal Interactions between Oligodendrocyte Precursor Cells and the Neurovascular Unit in Health and Disease

  2022cites this paper
• Molecular and functional heterogeneity in dorsal and ventral oligodendrocyte progenitor cells of the mouse forebrain in response to DNA damage

  2022cites this paper
• Thyroid Transcription Factor-1: Structure, Expression, Function and Its Relationship with Disease

  2021cites this paper
• Cell of all trades: oligodendrocyte precursor cells in synaptic, vascular, and immune function

  2021cites this paper
• Neuron–Oligodendrocyte Communication in Myelination of Cortical GABAergic Cells

  2021cites this paper
• The Impact of Fixation on the Detection of Oligodendrocyte Precursor Cell Morphology and Vascular Associations

  2021cites this paper
• Relationship between Blood Vessels and Migration of Neuroblasts in the Olfactory Neurogenic Region of the Rodent Brain

  2021cites this paper
• Oligodendrogenesis and myelin formation in the forebrain require platelet-derived growth factor receptor-alpha.

  2020cites this paper
• Wnt-Dependent Oligodendroglial-Endothelial Interactions Regulate White Matter Vascularization and Attenuate Injury.

  2020cites this paper
• Inactivation of HIF‐prolyl 4‐hydroxylases 1, 2 and 3 in NG2‐expressing cells induces HIF2‐mediated neurovascular expansion independent of erythropoietin

  2020cites this paper
• Poly(ester amide) microspheres are efficient vehicles for long-term intracerebral growth factor delivery and improve functional recovery after stroke

  2020cites this paper
• Neuronal and glial regulation of CNS angiogenesis and barriergenesis

  2020cites this paper
• Developmental cell death regulates lineage-related interneuron-oligodendroglia functional clusters and oligodendrocyte homeostasis

  2019cites this paper
• The cerebral cortex is a substrate of multiple interactions between GABAergic interneurons and oligodendrocyte lineage cells.

  2019cites this paper
• Neurovascular Interactions in the Nervous System.

  2019cites this paper
• Vascular regeneration in adult mouse cochlea stimulated by VEGF-A165 and driven by NG2-derived cells ex vivo.

  2019cites this paper
• Preterm intraventricular cerebral hemorrhage: role of cell-free hemoglobin

  2019cites this paper
• Defining the role of NG2-expressing cells in experimental models of multiple sclerosis. A biofunctional analysis of the neurovascular unit in wild type and NG2 null mice

  2019cites this paper
• Cortical and Commissural Defects Upon HCF‐1 Loss in Nkx2.1‐Derived Embryonic Neurons and Glia

  2019cites this paper
• Blood-to-brain communication in the hypothalamus for energy intake regulation.

  2019cites this paper
• Cortical developmental death: selected to survive or fated to die.

  2018cites this paper
• Neurovascular Communication during CNS Development.

  2018cites this paper
• NG2 Glia: Novel Roles beyond Re-/Myelination

  2018cites this paper
• Motor neurons control blood vessel patterning in the developing spinal cord

  2017cites this paper
• Prognostic relevance of NG2/CSPG4, CD44 and Ki-67 in patients with glioblastoma

  2017cites this paper
• Nkx2.1 regulates the generation of telencephalic astrocytes during embryonic development

  2017cites this paper
• Nkx2.1 regulates the proliferation and cell fate of telencephalic astrocytes during embryonic development

  2016cites this paper