The effect of brain-specific VEGF-C deletion on vascular morphology in the brain and skull

Vascular endothelial growth factor C (VEGF-C) promotes mainly lymphangiogenesis, but it can also stimulate angiogenesis by binding to VEGFR3 and VEGFR2 on endothelial cell surface. We studied VEGF-C expression by β-galactosidase staining in VegfcLacZ/+ mice. This revealed Vegfc expression in various parts of the brain. To investigate the role of VEGF-C in the brain, we generated Nestin-Cre; Vegfcfl/fl mice, in which we confirmed deletion of Vegfc. Nestin-Cre is expressed in neuronal and glial cell precursors, in which it mediates Cre-lox recombination of the floxed Vegfc allele. The objective of my study was to see if brain-specific deletion of Vegfc would affect the morphology of meningeal (dural) blood vessels or lymphatic vessels (mLV) in the central nervous system. Immunofluorescent staining was used to visualize the vasculature in dura, spinal column, pituitary gland and brain. The deletion caused no obvious effects on the blood vasculature in the analyzed tissues. However, male mice with Vegfc deletion displayed mLV hypoplasia, which was more severe than in females, and they also had swollen paws. Further immunofluorescence analysis of the ears, genotyping of the toes and qPCR analysis of Vegfc expression in the heart, lung and kidney indicated that Vegfc was deleted also outside of the nervous tissue. By searching published papers, we found that the Nestin-Cre transgenic mice can display sex-biased germline recombination of floxed alleles in multiple tissues if the Nestin-driven recombinase is expressed in gametes or too early during mouse development, which could be the case in our experiments. Thus, at present, we can conclude that the VEGF-C deletion did not affect blood vessels in the CNS, but we cannot yet be sure if VEGF-C deletion in neuronal and glial cells affects the mLVs.

Grantor dc:publisher

Helsingin yliopisto

Year dc:date.issued

2024

Author dc:creator

• Rolin, Tinja Emilia

• VEGF-C
• VEGFR3
• lymphangiogenesis
• blood vessels
• Nestin
• brain
• mouse
• meningeal lymphatic vessels

Statement dc:rights

• In Copyright 1.0

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10138/586637

OAI identifier oai:identifier

oai:helda.helsinki.fi:10138/586637