Vascular Regulation Of Neocortical Interneuron Production
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The neocortex contains glutamatergic excitatory neurons and GABAergic inhibitory interneurons. Extensive studies have revealed substantial insights into glutamatergic neuron production. However, our knowledge of the generation of GABAergic interneurons remains limited. Here we show that periventricular blood vessels regulate progenitor behaviour and neocortical interneuron production. Distinct from those in the dorsal telencephalon, radial glial progenitors (RGPs) in the ventral telencephalon responsible for producing neocortical interneurons progressively grow radial glial fibres anchored to periventricular vessels. Disrupting this robust progenitor-vessel interaction by selective removal of INTEGRIN ?1 in RGPs leads to a decrease in progenitor division, a loss of PARVALBUMIN-, but not SOMATOSTATIN-, expressing interneurons, and defective synaptic inhibition in the neocortex. Moreover, endothelial cell-specific deletion of stem cell factor results in similar defects in progenitor division and neocortical interneuron production. These results highlight a prominent interaction between RGPs and vessels crucial for proper production and function of neocortical interneurons.
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2015
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Brain development; Interneuron; Neural stem cell; Neurogenesis; Vascular niche
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Cell & Developmental Biology
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Doctor of Philosophy
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Government Document
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Attribution-NonCommercial-NoDerivatives 4.0 International
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dissertation or thesis