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      Cross-talk between blood vessels and neural progenitors in the developing brain

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          Abstract

          The formation of the central nervous system (CNS) involves multiple cellular and molecular interactions between neural progenitor cells (NPCs) and blood vessels to establish extensive and complex neural networks and attract a vascular supply that support their function. In this review, we discuss studies that have performed genetic manipulations of chick, fish and mouse embryos to define the spatiotemporal roles of molecules that mediate the reciprocal regulation of NPCs and blood vessels. These experiments have highlighted core functions of NPC-expressed ligands in initiating vascular growth into and within the neural tube as well as establishing the blood–brain barrier. More recent findings have also revealed indispensable roles of blood vessels in regulating NPC expansion and eventual differentiation, and specific regional differences in the effect of angiocrine signals. Accordingly, NPCs initially stimulate blood vessel growth and maturation to nourish the brain, but blood vessels subsequently also regulate NPC behaviour to promote the formation of a sufficient number and diversity of neural cells. A greater understanding of the molecular cross-talk between NPCs and blood vessels will improve our knowledge of how the vertebrate nervous system forms and likely help in the design of novel therapies aimed at regenerating neurons and neural vasculature following CNS disease or injury.

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          Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain.

          Neural stem cells (NSCs, B1 cells) are retained in the walls of the adult lateral ventricles but, unlike embryonic NSCs, are displaced from the ventricular zone (VZ) into the subventricular zone (SVZ) by ependymal cells. Apical and basal compartments, which in embryonic NSCs play essential roles in self-renewal and differentiation, are not evident in adult NSCs. Here we show that SVZ B1 cells in adult mice extend a minute apical ending to directly contact the ventricle and a long basal process ending on blood vessels. A closer look at the ventricular surface reveals a striking pinwheel organization specific to regions of adult neurogenesis. The pinwheel's core contains the apical endings of B1 cells and in its periphery two types of ependymal cells: multiciliated (E1) and a type (E2) characterized by only two cilia and extraordinarily complex basal bodies. These results reveal that adult NSCs retain fundamental epithelial properties, including apical and basal compartmentalization, significantly reshaping our understanding of this adult neurogenic niche.
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            Autocrine VEGF signaling is required for vascular homeostasis.

            Vascular endothelial growth factor (VEGF) is essential for developmental and pathological angiogenesis. Here we show that in the absence of any pathological insult, autocrine VEGF is required for the homeostasis of blood vessels in the adult. Genetic deletion of vegf specifically in the endothelial lineage leads to progressive endothelial degeneration and sudden death in 55% of mutant mice by 25 weeks of age. The phenotype is manifested without detectable changes in the total levels of VEGF mRNA or protein, indicating that paracrine VEGF could not compensate for the absence of endothelial VEGF. Furthermore, wild-type, but not VEGF null, endothelial cells showed phosphorylation of VEGFR2 in the absence of exogenous VEGF. Activation of the receptor in wild-type cells was suppressed by small molecule antagonists but not by extracellular blockade of VEGF. These results reveal a cell-autonomous VEGF signaling pathway that holds significance for vascular homeostasis but is dispensable for the angiogenic cascade.
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              A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution.

              The more than 1000-fold increase in the cortical surface without a comparable increase in its thickness during mammalian evolution is explained in the context of the radial-unit hypothesis of cortical development. According to the proposed model, cortical expansion is the result of changes in proliferation kinetics that increase the number of radial columnar units without changing the number of neurons within each unit significantly. Thus, mutation of a regulatory gene(s) that controls the timing and ratio of symmetric and asymmetric modes of cell divisions in the proliferative zone, coupled with radial constraints in the distribution of migrating neurons, could create an expanded cortical plate with enhanced capacity for establishing new patterns of connectivity that are validated through natural selection.
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                Author and article information

                Journal
                ppneurosig
                NS
                Neuronal Signal.
                Neuronal Signaling
                Neuronal Signal.
                Portland Press Ltd.
                2059-6553
                22 February 2018
                31 March 2018
                30 March 2018
                : 2
                : 1
                : NS20170139
                Affiliations
                UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, U.K.
                Author notes
                Correspondence: Christiana Ruhrberg ( c.ruhrberg@ 123456ucl.ac.uk )
                Article
                10.1042/NS20170139
                4d0449a2-e686-47e4-9661-e7d177f4870e
                © 2018 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 08 January 2018
                : 20 February 2018
                : 21 February 2018
                Page count
                Pages: 13
                Categories
                Review Articles
                Review Article
                28
                40
                10
                31
                47

                Neurology,Molecular medicine,Molecular biology,Neurosciences
                angiogenesis,blood brain barrier,central nervous system,embryogenesis,neurogenesis,neural stem cells

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