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Evolution of the VEGF-Regulated Vascular Network from a Neural Guidance System

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Abstract

The vascular network is closely linked to the neural system, and an interdependence is displayed in healthy and in pathophysiological responses. How has close apposition of two such functionally different systems occurred? Here, we present a hypothesis for the evolution of the vascular network from an ancestral neural guidance system. Biological cornerstones of this hypothesis are the vascular endothelial growth factor (VEGF) protein family and cognate receptors. The primary sequences of such proteins are conserved from invertebrates, such as worms and flies that lack discernible vascular systems compared to mammals, but all these systems have sophisticated neuronal wiring involving such molecules. Ancestral VEGFs and receptors (VEGFRs) could have been used to develop and maintain the nervous system in primitive eukaryotes. During evolution, the demands of increased morphological complexity required systems for transporting molecules and cells, i.e., biological conductive tubes. We propose that the VEGF–VEGFR axis was subverted by evolution to mediate the formation of biological tubes necessary for transport of fluids, e.g., blood. Increasingly, there is evidence that aberrant VEGF-mediated responses are also linked to neuronal dysfunctions ranging from motor neuron disease, stroke, Parkinson’s disease, Alzheimer’s disease, ischemic brain disease, epilepsy, multiple sclerosis, and neuronal repair after injury, as well as common vascular diseases (e.g., retinal disease). Manipulation and correction of the VEGF response in different neural tissues could be an effective strategy to treat different neurological diseases.

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Acknowledgments

Work in our laboratories was supported by grants from the British Heart Foundation (S.P.), The Wellcome Trust (S.P.), Heart Research UK (S.P.), and Ministry of Scientific Research of Italy, PRIN 2009 (M.A.).

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  1. Endothelial Cell Biology Unit, Institute of Molecular & Cellular Biology, LIGHT Laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK

    Sreenivasan Ponnambalam

  2. Department of Biochemistry and Molecular Biology, University of Catania Medical School, Viale Andrea Doria 6, 95125, Catania, Italy

    Mario Alberghina

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  1. Sreenivasan Ponnambalam
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Correspondence to Mario Alberghina.

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Ponnambalam, S., Alberghina, M. Evolution of the VEGF-Regulated Vascular Network from a Neural Guidance System. Mol Neurobiol 43, 192–206 (2011). https://doi.org/10.1007/s12035-011-8167-3

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  • DOI: https://doi.org/10.1007/s12035-011-8167-3

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