2021
DOI: 10.3390/ijms22105321
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Lack of WWC2 Protein Leads to Aberrant Angiogenesis in Postnatal Mice

Abstract: The WWC protein family is an upstream regulator of the Hippo signalling pathway that is involved in many cellular processes. We examined the effect of an endothelium-specific WWC1 and/or WWC2 knock-out on ocular angiogenesis. Knock-outs were induced in C57BL/6 mice at the age of one day (P1) and evaluated at P6 (postnatal mice) or induced at the age of five weeks and evaluated at three months of age (adult mice). We analysed morphology of retinal vasculature in retinal flat mounts. In addition, in vivo imaging… Show more

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Cited by 5 publications
(5 citation statements)
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“…Substantial Wwc2 gene expression was also present in endothelial and vascular/leptomeningeal cells in the hippocampus and cortex (Fig. 1C), consistent with studies demonstrating a critical role for WWC2 in vascular development 33,34 . Many, though not all, forebrain neurons co-express KIBRA and WWC2, and their gene expression is positively correlated in excitatory hippocampal cell types (Fig.…”
Section: Resultssupporting
confidence: 87%
“…Substantial Wwc2 gene expression was also present in endothelial and vascular/leptomeningeal cells in the hippocampus and cortex (Fig. 1C), consistent with studies demonstrating a critical role for WWC2 in vascular development 33,34 . Many, though not all, forebrain neurons co-express KIBRA and WWC2, and their gene expression is positively correlated in excitatory hippocampal cell types (Fig.…”
Section: Resultssupporting
confidence: 87%
“…3,14 Due to their common structure and binding partners, WWC proteins were shown to possess a redundant function if they are expressed in the same tissue at the same time. 3,13,14 However, Wwc2 has an unique impact on murine embryonal angiogenesis 14 and postnatal ocular angiogenesis, 38 pointing to its crucial role in early embryonic development when the other Wwc family members are not or only weakly expressed.…”
Section: Discussionmentioning
confidence: 99%
“…This process removes excess vessels from the vascular network by regulating the expression of connective tissue growth factor (CTGF) and actin polymerization [ 28 ]. Depletion of WW-and-C2-domain-containing (WWC2), an upstream regulator of the Hippo signaling pathway and inhibitor of YAP/TAZ, leads to the hyperproliferation of endothelial cells with enlarged sprouting areas and increased tip cell numbers in the ocular vessels of postnatal mice [ 8 ].…”
Section: Discussionmentioning
confidence: 99%
“…The activity of YAP and TAZ is inhibited by the large tumor suppressor (LATS) kinases which phosphorylate YAP and TAZ at specific serine residues and prevent their nuclear translocation. Although there is evidence showing that the Hippo signaling pathway controls the survival and activity of mature endothelial cells [ 7 , 8 , 9 ], the regulatory roles of YAP and TAZ in EPC functions are still largely unknown.…”
Section: Introductionmentioning
confidence: 99%