Fibroblast-Specific Deletion of Yap/Taz Impairs Mouse Postnatal Dermal Development by Diminishing Collagenous Matrix

The transcriptional co-activators YAP and TAZ are key regulators of cell proliferation, apoptosis, and differentiation, thereby maintaining tissue homeostasis and controlling organ size. While their roles in epithelial cancers and fibrosis are well established, their involvement in the physiological regulation of the dermal extracellular matrix (ECM) by fibroblasts is less understood. Here, we investigated the role of Yap/Taz during postnatal development of the dermal ECM. During postnatal growth, mouse skin steadily undergoes significant surface expansion. Postnatal deletion of Yap/Taz in dermal fibroblasts, the primary cells responsible for dermal ECM homeostasis, significantly impaired dermal ECM maturation, as evidenced by marked deficiencies in collagen expression, deposition, and organization. Isolated fibroblasts from Yap/Taz knockout mice showed reduced expression of Yap/Taz target genes ( Ccn1, Ccn2 , Col1a1 ), which were rescued by reintroduction of active Yap/Taz . RNA-seq, spatial transcriptomics, and proteomics of Yap/Taz knockout skin revealed substantial downregulation of ECM-related genes, including type I ( Col1a1, Col1a2) and type III ( Col1a3 ) collagens, which together constitute more than 90% of the skin's collagen content. Mechanistically, deletion of Yap/Taz impaired mouse dermal maturation, at least in part through suppression of TGF-β/Smad signaling, the primary pathway governing fibroblast collagen synthesis. These findings demonstrate that YAP/TAZ are essential for postnatal dermal ECM homeostasis.