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Blood Vessels As a Scaffold for Neuronal Migration

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Blood Vessels As a Scaffold for Neuronal Migration Neurochemistry International 126 (2019) 69–73 Contents lists available at ScienceDirect Neurochemistry International journal homepage: www.elsevier.com/locate/neuint Blood vessels as a scaffold for neuronal migration T ∗ Teppei Fujiokaa,b,1, Naoko Kanekoa,1, Kazunobu Sawamotoa,c, a Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 467-8601, Japan b Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 467-8601, Japan c Division of Neural Development and Regeneration, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8585, Japan ARTICLE INFO ABSTRACT Keywords: Neurogenesis and angiogenesis share regulatory factors that contribute to the formation of vascular networks Neuronal migration and neuronal circuits in the brain. While crosstalk mechanisms between neural stem cells (NSCs) and the vas- Blood vessel culature have been extensively investigated, recent studies have provided evidence that blood vessels also play Ventricular-subventricular zone an essential role in neuronal migration in the brain during development and regeneration. The mechanisms of Neurogenesis the neuronal migration along blood vessels, referred to as “vascular-guided migration,” are now being eluci- Angiogenesis dated. The vascular endothelial cells secrete soluble factors that attract and promote neuronal migration in Brain regeneration collaboration with astrocytes that enwrap the blood vessels. In addition, especially in the adult brain, the blood vessels serve as a migration scaffold for adult-born immature neurons generated in the ventricular-sub- ventricular zone (V-SVZ), a germinal zone surrounding the lateral ventricles. The V-SVZ-derived immature neurons use the vascular scaffold to assist their migration toward an injured area after ischemic stroke, and contribute to neuronal regeneration. Here we review the current knowledge about the role of vasculature in neuronal migration and the molecular mechanisms controlling this process. While most of this research has been done in rodents, a comprehensive understanding of vasculature-guided neuronal migration could contribute to new therapeutic approaches for increasing new neurons in the brain after injury. 1. Introduction integrated into the circuitry to modify or regenerate pre-existing neu- ronal circuits. In this review, we describe the latest findings on vascu- The regulation of cellular migration is fundamental not only to lature-guided neuronal migration. While most of this research has been morphogenesis during development, but also to the maintenance and performed in rodents, we also discuss the implications of these findings modification of adult tissues and organs. In the developing brain, im- for therapeutic approaches involving neuronal regeneration. mature neurons generated in the germinal zones migrate to their final destinations, in a manner tightly regulated by multiple cell-intrinsic and 2. Role of vasculature in cellular migration extrinsic mechanisms. Among them, common instructive cues and cross-talk signals between neurogenesis and angiogenesis play essential Cells exhibit different migration modes depending on the cell type roles in establishing a complex and functional neuronal network that is and context. Recent studies using time-lapse imaging techniques with supported by vascularization. transgenic mice and fish revealed a unique migrating mode in which Even after the developmental period, neurogenesis still occurs in cells move along blood vessels. In embryonic development, vasculature- restricted brain regions. The ventricular-subventricular zone (V-SVZ) is guided migration has been reported for endothelial cells that form the the largest germinal zone in adult mammals. The V-SVZ-derived im- lymphatic vascular system in the zebrafish trunk (Bussmann et al., mature new neurons, called neuroblasts, migrate into the olfactory bulb 2010) and for oligodendrocyte precursor cells (OPCs) in mice (Tsai under physiological conditions and toward a lesion in cases of brain et al., 2016). In adult rodents after peripheral nerve transection, the injury, such as ischemic stroke. These processes are closely associated Schwann cells enwrapping peripheral nerve axons de-differentiate and with angiogenesis and/or its regulatory factors. After the termination of migrate along blood vessels toward the lesion, where they promote migration, the neuroblasts differentiate into mature neurons and are axonal regeneration (Cattin et al., 2015). Highly invasive and ∗ Corresponding author. Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. E-mail address: [email protected] (K. Sawamoto). 1 equal contribution. https://doi.org/10.1016/j.neuint.2019.03.001 Received 18 December 2018; Received in revised form 27 February 2019; Accepted 2 March 2019 Available online 06 March 2019 0197-0186/ © 2019 Elsevier Ltd. All rights reserved. T. Fujioka, et al. Neurochemistry International 126 (2019) 69–73 Abbreviations NSCs neural stem cells OPCs oligodendrocyte precursor cells Ang1 angiopoietin 1 RMS rostral migratory stream BDNF brain-derived neurotropic factor SDF1 stromal cell-derived factor 1 CXCR4 C-X-C chemokine receptor type 4 VEGF vascular endothelial growth factor ECM extracellular matrix V-SVZ ventricular-subventricular zone GABA gamma-aminobutyric acid metastasizing tumor cells in malignant glioma and melanoma (Farin reported mainly in the brain, suggesting that brain-specific anatomical et al., 2006; Lugassy and Barnhill, 2007), and as described below, V- and/or functional properties, such as the presence of astrocytic endfeet SVZ-derived neuroblasts also migrate along blood vessels in the brain. that almost completely enwrap the blood vessels, might be involved in Although the molecular mechanisms regulating the association of these this migration. It is also possible that some environmental factors or cells with blood vessels remain largely unknown, the vasculature ap- conditions specific to the adult brain increase the need for the vascular pears to contribute to their active migration. support of migrating cells. Blood vasculature supports cell migration in at least two ways: 1) by transporting oxygen and nutrients, and secreting soluble factors, which 3. Vasculature-guided neuronal migration in the embryonic brain provide an appropriate microenvironment for cellular migration, and 2) by serving as a physical scaffold and providing adhesion-dependent During cortical development, excitatory neurons are produced by signals for migration, as well as proliferation, differentiation, and sur- radial glia, embryonic neural stem cells (NSCs), in the ventricular zone vival to the cells. In adult animals, vasculature-guided migration is of the dorsal telencephalon. The neurons then migrate radially along Fig. 1. Schematic illustration of neuronal migration along the vasculature. (A) In the embryonic brain, GABAergic interneurons generated in the ventral telencephalon migrate tangentially toward the developing neocortex for a long distance along blood vessels. Diffusible factors secreted from vascular endothelial cells, such as GABA and VEGF, promote migration of the interneurons in close association with vascular networks. (B) In the RMS in the developing neonatal brain, V-SVZ-derived neuroblasts migrate tangentially toward the OB through astrocytic tunnels referred to as glial tubes. Blood vessels running parallel to the RMS, which develop postnatally under the control of VEGF secreted by the RMS-forming astrocytes, assist the neuroblasts as migration scaffolds. (C) In the adult RMS, endothelial cell-derived BDNF promotes neuronal migration toward the OB. RMS astrocytes modulate the local concentration of BDNF by capturing it with the high-affinity receptor TrkB, while neuroblasts express a low-affinity BDNF receptor p75NTR. This mechanism involving BDNF also regulates vasculature-guided neuronal migration in the striatum in the post-stroke brain. (D, E) In the striatum in the post-stroke brain, SDF1 secreted from endothelial cells and reactive astrocytes promotes neuronal migration along blood vessels. The interaction of β1 integrin expressed in neuroblasts and laminin, an extracellular matrix protein composing the vascular basal lamina, facilitates neuroblast migration using vascular scaffolds. MGE: medial ganglionic eminence; LGE: lateral ganglionic eminence; Ncx: neocortex; OB: olfactory bulb; RMS: rostral migratory stream; V-SVZ: ventricular-sub- ventricular zone; GABA: gamma-aminobutyric acid; VEGF: vascular endothelial growth factor; BDNF: brain-derived neurotropic factor; SDF1: stromal cell-derived factor 1; CXCR4: C-X-C chemokine receptor type 4. 70 T. Fujioka, et al. Neurochemistry International 126 (2019) 69–73 the long basal fibers of mother radial glia to reach their final destination guidance (Le Magueresse et al., 2012). A similar association between (Kawauchi, 2015; Rakic, 2007). On the other hand, gamma-aminobu- migrating neuroblasts and vasculature is observed in the adult zebrafish tyric acid (GABA)ergic inhibitory interneurons originate in the ventral brain (Kishimoto et al., 2011). Therefore, the migration of V-SVZ-de- telencephalon and migrate tangentially toward the cortex over long rived neuroblasts in the postnatal brain is closely associated with blood distances (Marin, 2013; Guo and Anton, 2014) and are associated with vessels
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