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  EphrinB2 regulates VEGFR2 during dendritogenesis and hippocampal circuitry development

Harde, E., Nicholson, L., Furones Cuadrado, B., Bissen, D., Wigge, S., Urban, S., et al. (2019). EphrinB2 regulates VEGFR2 during dendritogenesis and hippocampal circuitry development. Elife, 8. doi:10.7554/eLife.49819.

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Harde, E., Author
Nicholson, L., Author
Furones Cuadrado, B., Author
Bissen, D., Author
Wigge, S., Author
Urban, S., Author
Segarra, M., Author
Ruiz de Almodovar, C., Author
Acker-Palmer, Amparo1, Author              
Affiliations:
1Neurovascular interface Group, Max Planck Institute for Brain Research, Max Planck Society, ou_2461707              

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Free keywords: Animals CA3 Region, Hippocampal Dendrites/*metabolism Dendritic Spines/metabolism Endothelial Cells/metabolism Ephrin-B2/genetics/*metabolism Gene Expression Regulation, Developmental Hippocampus/*metabolism Long-Term Potentiation/physiology Mice Neurogenesis/genetics/*physiology Neuronal Plasticity/physiology Neurons/physiology Synapses/physiology Transcriptome Vascular Endothelial Growth Factor Receptor-2/genetics/*metabolism *dendritic arborisation *developmental biology *hippocampal development *mouse *neuroscience *neurovascular link
 Abstract: Vascular endothelial growth factor (VEGF) is an angiogenic factor that play important roles in the nervous system, although it is still unclear which receptors transduce those signals in neurons. Here, we show that in the developing hippocampus VEGFR2 (also known as KDR or FLK1) is expressed specifically in the CA3 region and it is required for dendritic arborization and spine morphogenesis in hippocampal neurons. Mice lacking VEGFR2 in neurons (Nes-cre Kdr(lox/-)) show decreased dendritic arbors and spines as well as a reduction in long-term potentiation (LTP) at the associational-commissural - CA3 synapses. Mechanistically, VEGFR2 internalization is required for VEGF-induced spine maturation. In analogy to endothelial cells, ephrinB2 controls VEGFR2 internalization in neurons. VEGFR2-ephrinB2 compound mice (Nes-cre Kdr(lox/+) Efnb2(lox/+)) show reduced dendritic branching, reduced spine head size and impaired LTP. Our results demonstrate the functional crosstalk of VEGFR2 and ephrinB2 in vivo to control dendritic arborization, spine morphogenesis and hippocampal circuitry development.

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 Dates: 2019-12-24
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: Other: 31868584
DOI: 10.7554/eLife.49819
ISSN: 2050-084X (Electronic)2050-084X (Linking)
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Title: Elife
Source Genre: Journal
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Pages: - Volume / Issue: 8 Sequence Number: - Start / End Page: - Identifier: -