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Vascular pattern of the dentate gyrus is regulated by neural progenitors

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Abstract

Neurogenesis is a vital process that begins during early embryonic development and continues until adulthood, though in the latter case, it is restricted to the subventricular zone and the subgranular zone of the dentate gyrus (DG). In particular, the DG’s neurogenic properties are structurally and functionally unique, which may be related to its singular vascular pattern. Neurogenesis and angiogenesis share molecular signals and act synergistically, supporting the concept of a neurogenic niche as a functional unit between neural precursors cells and their environment, in which the blood vessels play an important role. Whereas it is well known that vascular development controls neural proliferation in the embryonary and in the adult brain, by releasing neurotrophic factors; the potential influence of neural cells on vascular components during angiogenesis is largely unknown. We have demonstrated that the reduction of neural progenitors leads to a significant impairment of vascular development. Since VEGF is a potential regulator in the neurogenesis–angiogenesis crosstalk, we were interested in assessing the possible role of this molecule in the hippocampal neurovascular development. Our results showed that VEGF is the molecule involved in the regulation of vascular development by neural progenitor cells in the DG.

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Acknowledgements

We thank Dr. A. Barco for providing us Nes-Cre mouse strain. This work was supported by Spanish State Research Agency, through the “Severo Ochoa” Program for Centers of Excellence in R&D (ref. SEV- 2013-0317), by Economy and Competitivity Ministry through Fondos FEDER (SAF2014-59347-C2-1-R), by Generalitat Valenciana Prometeo II Grant (2014/014), by Instituto de Salud Carlos III (RD16/001/0010) (Co-funded by European Regional Development Fund/European Social Fund) and Todos con Natalia Niemann Pick C Association (2016/00084/001).

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  1. Ana Pombero and Raquel Garcia-Lopez have contributed equally to this work and are listed alphabetically.

Authors and Affiliations

  1. Instituto de Neurociencias, UMH-CSIC, Campus de San Juan, 03550, Alicante, Spain

    Salvador Martinez

  2. IMIB-Arrixaca, University of Murcia, Av. Teniente Flomesta, 5, 30003, Murcia, Spain

    Ana Pombero, Raquel Garcia-Lopez & Alicia Estirado

  3. Centro de Investigación Biomédica En Red en Salud Mental (CIBERSAM), Madrid, Spain

    Salvador Martinez

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  1. Ana Pombero
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  2. Raquel Garcia-Lopez
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  4. Salvador Martinez
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Correspondence to Salvador Martinez.

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Funding

This work was supported by Spanish State Research Agency, through the “Severo Ochoa” Program for Centers of Excellence in R&D (ref. SEV- 2013 − 0317), by Economy and Competitivity Ministry through Fondos FEDER (SAF2014-59347-C2-1-R), by Generalitat Valenciana Prometeo II Grant (2014/014), by Instituto de Salud Carlos III (RD16/001/0010) (Co-funded by European Regional Development Fund/European Social Fund), and Todos con Natalia Niemann Pick C Association (2016/00084/001)

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The authors declare that they have no conflict of interest.

Ethical approval

All animal experimental assays were performed in compliance with the Spanish and European Union laws on animal care in experimentation (Council Directive 86/609/EEC) and approved by the Animal Experimentation Ethics Committee of our University. This article does not contain any studies with human participants performed by any of the authors.

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Supplementary Figure 1

. Analysis of cre activity in the cortex and the hippocampus. CD13 (green color) was used as a pericyte marker together with RFP (red color) used as a reporter of cre activity. No double labeling was detected in double immunohistochemistry for CD13/RFP in Cx (A-C), DMS (D-F), CA (G-I), and DG (J-L). Scale bar is 25 µm (TIF 44947 KB)

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Pombero, A., Garcia-Lopez, R., Estirado, A. et al. Vascular pattern of the dentate gyrus is regulated by neural progenitors. Brain Struct Funct 223, 1971–1987 (2018). https://doi.org/10.1007/s00429-017-1603-z

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