Mural-Endothelial cell-cell interactions stabilize the developing zebrafish dorsal aorta

Abstract

Mural cells (vascular smooth muscle cells and pericytes) play an essential role in the development of the vasculature, promoting vascular quiescence and long-term vessel stabilization through their interactions with endothelial cells. However, the mechanistic details of how mural cells stabilize vessels are not fully understood. We have examined the emergence and functional role of mural cells investing the dorsal aorta during early development using the zebrafish. Consistent with previous literature, our data suggest that cells ensheathing the dorsal aorta emerge from a sub-population of cells in the adjacent sclerotome. Inhibition of mural cell recruitment to the dorsal aorta through disruption of pdgfr signaling leads to a reduced vascular basement membrane, which in turn results in enhanced dorsal aorta vessel elasticity and failure to restrict aortic diameter. Our results provide direct in vivo evidence for a functional role for mural cells in patterning and stabilization of the early vasculature through production and maintenance of the vascular basement membrane to prevent abnormal aortic expansion and elasticity.

Robust differentiation of human pluripotent stem cells into endothelial cells via temporal modulation of ETV2 with modified mRNA

“…It is important to note that although co-transplantation with MSCs facilitates engraftment, h-iECs derived from the S1-modETV2 protocol were also able to engraft and form perfused vessels when We also examined the presence of mural cell investment around the newly-formed human vessels, a hallmark of proper vessel maturation and stabilization (24). There was a striking difference between h-iECs generated with the S1-modETV2 protocol and those generated with the early modETV2 with regard to perivascular investment ( Fig.…”

Endothelial cells and organ function: applications and implications of understanding unique and reciprocal remodelling

“…Animal experiments frequently use zebrafish as a model system, since their transparent nature enables complex in vivo microscopic analysis and real‐time visualization of cellular behaviour in situ . However, findings are not always translatable into humans . Knockout studies in mice using Cre recombinase under endothelial‐specific promoters are possible, but global phenotypes are often difficult to interpret or may even obscure organ‐specific effects.…”

Frizzled 4 regulates ventral blood vessel remodeling in the zebrafish retina

“…The localization pattern of fzd4 mRNA is reminiscent of pericytes, a type of perivascular cell associated with capillaries and involved in regulating vascular structure, dynamics and homeostasis. 29,30 The presence of pericytes has been previously reported, by transmission electron microscopy, as a component of the adult zebrafish retinal vasculature 23 and, more recently, by the presence of platelet-derived growth factor receptor ß (pdgfrß) positive cells surrounding the hyaloid vasculature of 72 hpf fish larvae. 31 In order to confirm the presence and identity of pericytes in adult retinas, we performed single fluorescent ISH staining with two known pericyte markers, notch3 31 and pdgfrß mRNA.…”