The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Cortical and retinal defects caused by dosage-dependent reductions in VEGF-A paracrine signaling
Open accessAbstract
To determine the function of VEGF-A in nervous system development, we have utilized the Nestin promoter-driven Cre recombinase transgene, in conjunction with a conditional and hypomorphic VEGF-A allele, to lower VEGF-A activity in neural progenitor cells. Mice with intermediate levels of VEGF-A activity showed decreased blood vessel branching and density in the cortex and retina, resulting in a thinner retina and aberrant structural organization of the cortex. Severe reductions in VEGF-A led to decreases in vascularity and subsequent hypoxia, resulting in the specific degeneration of the cerebral cortex and neonatal lethality. Decreased neuronal proliferation and hypoxia was evident at E11.5, leading to increased neuronal apoptosis in the cortex by E15.5. In order to address whether the observed changes in the structural organization of the nervous system were due to a direct and autocrine role of VEGF-A on the neural population, we conditionally inactivated the main VEGF-A receptor, Flk1, specifically in neuronal lineages, by using the Nestin Cre transgene. The normality of these mice ruled out the possibility that VEGF-A/Flk1 signaling has a significant autocrine role in CNS development. VEGF-A dosage is therefore a critical parameter regulating the density of the vascular plexus in the developing CNS that is in turn a key determinant in the development and architectural organization of the nervous system.
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Cites
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Development, maintenance and disruption of the blood-brain barrier
Obermeier, B., Daneman, R., & Ransohoff, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3407 · Cited by 2,452
Fantin, A., Vieira, J. M., Gestri, G., Denti, L., Schwarz, Q., Prykhozhij, S., Peri, F., Wilson, S. W., & Ruhrberg, C. (2010) · Blood · doi:10.1182/blood-2009-12-257832 · Cited by 1,153
Endothelial cells and VEGF in vascular development
Coultas, L., Chawengsaksophak, K., & Rossant, J. (2005) · Nature · doi:10.1038/nature04479 · Cited by 1,016
From angiogenesis to neuropathology
Greenberg, D. A., & Jin, K. (2005) · Nature · doi:10.1038/nature04481 · Cited by 532
Role and Therapeutic Potential of VEGF in the Nervous System
Ruiz de Almodovar, C., Lambrechts, D., Mazzone, M., & Carmeliet, P. (2009) · Physiological Reviews · doi:10.1152/physrev.00031.2008 · Cited by 448
Metadata
- Authors
- Haigh, J. J., Morelli, P. I., Gerhardt, H., Haigh, K., Tsien, J., Damert, A., Miquerol, L., Muhlner, U., Klein, R., Ferrara, N., Wagner, E. F., Betsholtz, C., & Nagy, A.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 262
- Issue
- 2
- Pages
- 225-241
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W1992112653
- Cited by
- 272
- References
- 52
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Haigh, J. J., Morelli, P. I., Gerhardt, H., Haigh, K., Tsien, J., Damert, A., Miquerol, L., Muhlner, U., Klein, R., Ferrara, N., Wagner, E. F., Betsholtz, C., & Nagy, A. (2003). Cortical and retinal defects caused by dosage-dependent reductions in VEGF-A paracrine signaling. Developmental Biology. https://doi.org/10.1016/s0012-1606(03)00356-7
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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