135 Transcription coactivators YAP and TAZ are essential for postnatal maturation of the dermal extracellular matrix in mouse skin

YAP and TAZ are critical downstream effectors of the hippo signaling pathway, which play pivotal roles in controlling organ size maintaining tissue homeostasis. Although dysregulation YAP/TAZ has been linked to various human diseases their role dermal extracellular matrix (ECM) regulation remains largely unknown. Here, we describe mouse ECM maturation during early postnatal development We find that from birth (P0) day 20 (P20), skin surface area increases 6-fold (N=6). This rapid expansion occurs at a linear rate, approximately 500mm2 3000mm2. Interestingly, total number fibroblasts remained nearly constant with 0.9x108 fibroblasts/mouse P0 P20 (N=15), resulting decreased density 1.5x106/mm3 0.3x106/mm3, between (N=15). To explore maturation, generated mice allowed conditional deletion fibroblasts, major producing cells skin, by Cre recombinase, under control platelet-derived growth factor receptor-alpha promoter (pdgfra-CreER;Yapf/f;Tazf/f). knockout Yap/Taz P3 pdgfra-CreER;Yapf/f;Tazf/f sex-matched littermates were topically treated 4-OH tamoxifen (10 mg/ml) for five consecutive days, back was harvested P20. Fibroblast-specific significantly impaired collagen fibril production, deposition, maturation. Dermal type I gene expression reduced 69%, RNA-seq/Gene Ontology (GO) analysis whole revealed altered 2668 genes (1466 upregulated, 1202 downregulated). Notably, pathway negatively enriched, whereas cytokines inflammatory response positively enriched. These data indicate plays