ausblenden:
Schlagwörter:
-
Zusammenfassung:
Serum Response Factor (SRF) is a ubiquitously expressed, essential transcription factor known to regulate the transcription of about 1000 genes. Recent work performed in our group showed that ablation of SRF in endothelial cells (ECs) leads to formation of hemorrhages in the neonatal murine brain and microaneurysms in the neonatal murine retina. Despite the established role of SRF in the vascular system, no functional analyses of SRF activity has so far been performed in pericytes. Pericytes are essential cellular components of the microvasculature with the main task of providing structural support for ECs. They play important roles in angiogenesis, vessel stabilization and homeostasis. To investigate any potential contributions of SRF to postnatal pericyte development in the murine retina, we performed phenotypic characterization of existing Srf-flex1::Pdgfbr-CreERT2 mice, which permit conditional deletion within the Srf gene locus in pericytes. Our observations of the vascular bed showed a decrease in the vessel area and branching points in mice with SRF-ablated pericytes. Moreover, further analyses showed local breakdowns of the blood retina barrier and massive depositions of collagen IV, arguing for instable blood vessels. Interestingly, the pericyte coverage of blood vessels is significantly reduced and – at later stages of postnatal development - artery venous malformations (AVMs) can be observed. Overall, our analysis indicates an important role of SRF in pericytes.
