Diverse roles for VEGF-A in the nervous system

Mackenzie, Francesca E.; Ruhrberg, Christiana

doi:10.1242/dev.072348

Cited by 250 publications

(198 citation statements)

References 129 publications

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“…Angiogenic factors, especially vascular endothelial growth factor (VEGF), are now known to play roles in neurogenesis and migration 27 . Endothelial tip cells guide outgrowing capillaries in response to gradients of extracellular, matrix-bound VEGF.…”

mentioning

confidence: 99%

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

et al. 2014

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During the development of the cerebral cortex, Cajal-Retzius (CR) cells settle in the preplate and coordinate the precise growth of the neocortex. Indeed, CR cells migrate tangentially from specific proliferative regions of the telencephalon (for example, the cortical hem (CH)) to populate the entire cortical surface. This is a very finely tuned process regulated by an emerging number of factors that has been sequentially revealed in recent years. However, the putative participation of one of the major families of axon guidance molecules in this process, the Semaphorins, was not explored. Here we show that Semaphorin-3E (Sema3E) is a natural negative regulator of the migration of PlexinD1-positive CR cells originating in the CH. Our results also indicate that Sema3E/PlexinD1 signalling controls the motogenic potential of CR cells in vitro and in vivo. Indeed, absence of Sema3E/PlexinD1 signalling increased the migratory properties of CR cells. This modulation implies negative effects on CXCL12/CXCR4 signalling and increased ADF/Cofilin activity.

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mentioning

confidence: 99%

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

et al. 2014

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“…These factors induce endothelial cell differentiation and guide their migrations as they undergo morphological changes to form blood vessels (Rousseau et al, 2000;Poole et al, 2001;Zachary et al, 2005;Lamalice et al, 2006;Koch and Claesson-Welsh, 2012). Their functions outside angiogenesis are not as well characterised; however, Drosophila PVF-1 has a role in border cell migration in Drosophila ovaries (McDonald et al, 2003;Mackenzie and Ruhrberg, 2012) and VEGF can act as a guidance cue by attracting commissural axons to the floor plate of the spinal cord (Ruiz de Almodovar et al, 2011) and by guiding migration of nerve cell soma (Schwarz et al, 2004). C. elegans PVF-1 is a secreted protein able to bind human VEGFR1 and VEGFR2, and induce vascular development in chick embryos and capillary tube formation in HUVEC cultures (Tarsitano et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

C. elegansPVF-1 inhibits permissive UNC-40 signalling through CED-10 GTPase to position the male ray 1 sensillum

et al. 2013

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Graded distributions of netrin and semaphorin guidance cues convey instructive polarity information to migrating cells and growth cones, but also have permissive (i.e. non-polarity determining) functions in mammalian development and repair. The permissive functions of these cues are largely uncharacterised at a molecular level. We found previously that UNC-6 (netrin) signals permissively through UNC-40 (DCC) and UNC-5 receptors to prevent anterior displacement of the ray 1 sensillum in the C. elegans male tail. UNC-6/UNC-40 signalling functions in parallel with SMP-1 (semaporin 1)/PLX-1 (plexin) signalling to prevent this defect. Here, we report that a deletion allele of pvf-1, which encodes a VEGF-related protein, causes no ray 1 defects, but enhances ray 1 defects of a plx-1 mutant, and unexpectedly also suppresses unc-6(ev400)-null mutant ray 1 defects. These mutant ray 1 inductive and suppressive effects are mimicked by the ability of unc-40(+) and ced-10(gain-of-function) multi-copy transgene arrays to induce ray 1 defects or suppress unc-6 mutant ray 1 defects, depending on their dosage, suggesting the pvf-1 mutation causes UNC-40 overactivity that interferes with signalling but is partially sensitive to UNC-6. Additional data suggest PVF-1 functions through four VEGF receptor-related proteins and inhibits only CED-10 (a GTPase), but not MIG-2-dependent UNC-40 activity, even though UNC-40 functions through both GTPases to position ray 1. pvf-1 and receptor mutant ray 1 defects are rescued by transgenes expressing mouse VEGF164 and human VEGF receptors, respectively. These data report the first case of VEGF-induced inhibition of the netrin signalling and a molecular conservation of VEGF function from worms to humans.

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“…VEGFA and VEGFRs are principal signaling pathways for proliferation of endothelial cells in the developing vasculature (Gerhardt et al 2003, Mackenzie & Ruhrberg 2012.…”

Section: Expression Of Vegfa and Vegfrsmentioning

confidence: 99%

“…Proliferation of endothelial cells is mainly regulated by the signaling of VEGFA and VEGFR2 in the developing vasculature (Gerhardt et al 2003, Somanath et al 2009). The expression level of total Vegfa mRNA is high during early embryonic period but it gradually decreases along with brain maturation (Ng et al 2001, Mackenzie & Ruhrberg 2012. It is also known that the expression pattern of the VEGFA isoform is different depending on developmental stages and tissues.…”

Section: Continuous Angiogenesismentioning

confidence: 99%

VEGF-dependent and PDGF-dependent dynamic neurovascular reconstruction in the neurohypophysis of adult mice

Furube¹,

Mannari²,

Morita³

et al. 2014

Journal of Endocrinology

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Hypothalamo-neurohypophysial system (HNS) releases arginine vasopressin (AVP) and oxytocin (OXT) from axonal terminals of the neurohypophysis (NH) into blood circulation for controlling body fluid homeostasis and lactation. Chronic osmotic and suckling stimulations have been shown to cause neurovascular and neuroglial reconstruction in the NH of adult mammals and no study has been reported for vascular dynamics. The aim of this study was to elucidate the occurrence of continuous angiogenesis and growth factor-dependent neurovascular reconstruction in the NH of adult mice. Active proliferation of endothelial cells and oligodendrocyte progenitor cells (OPCs) was observed using the immunohistochemistry of bromodeoxyuridine and Ki-67. Vascular endothelial growth factor A (VEGFA) and VEGF receptor 2 (VEGFR2 (KDR)) were highly expressed at pituicytes and endothelial cells respectively. Moreover, prominent expression of platelet-derived growth factor B (PDGFB) and PDGF receptor beta was observed at OXT-containing axonal terminals and pericytes respectively. Administration of the selective tyrosine kinase inhibitor AZD2171 for VEGFRs and STI571 for PDGFRs significantly decreased proliferation of endothelial cells and OPCs. Moreover, AZD2171 treatment decreased vascular density by facilitating apoptosis of endothelial cells and the withdrawal of its treatment led to remarkable rebound proliferation of endothelial cells, so that vascular density rapidly returned to normal levels. AZD2171 decreased the density of both AVP-and OXT-containing axonal terminals, whereas STI571 selectively decreased the density of AVP-containing ones. Thus, this study demonstrates that the signaling pathways of VEGF and PDGF are crucial mediators for determining proliferation of endothelial cells and OPCs and the density of AVP-and OXT-containing axonal terminals in the HNS.

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Diverse roles for VEGF-A in the nervous system

Cited by 250 publications

References 129 publications

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

C. elegansPVF-1 inhibits permissive UNC-40 signalling through CED-10 GTPase to position the male ray 1 sensillum

VEGF-dependent and PDGF-dependent dynamic neurovascular reconstruction in the neurohypophysis of adult mice

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