摘要：SummaryConnective tissue growth factor (CTGF) or cellular communication network 2 (CCN2) is a matricellular protein essential for normal embryonic development and tissue repair. CTGF exhibits cell- and context-dependent activities, but CTGF function in vascular development and barrier function is unknown. We show that endothelial cells (ECs) are one of the major cellular sources of CTGF in the developing and adult retinal vasculature. Mice lackingCTGFexpression either globally or specifically in ECs exhibit impaired vascular cell growth and morphogenesis and blood barrier breakdown. The global molecular signature of CTGF includes cytoskeletal and extracellular matrix protein, growth factor, and transcriptional co-regulator genes such asyes-associated protein(YAP). YAP, itself a transcriptional activator ofCTGF, mediates several CTGF-controlled angiogenic and barriergenic transcriptional programs. Re-expression ofYAPrescues, at least partially, angiogenesis and barriergenesis inCTGFmutant mouse retinas. Thus, the CTGF-YAP regulatory loop is integral to retinal vascular development and barrier function.Graphical AbstractDisplay OmittedHighlights•CTGF has a strong and persistent expression in the retinal vasculature•Mice lacking CTGF exhibit defects in angiogenesis and blood barrier integrity•CTGF-targeted genes include matrix, growth, and transcription co-factors like YAP•YAP re-expression partly rescues angiogenic and barriergenic defects of CTGF lossMolecular Biology; Cell Biology; Transcriptomics
