⑵Notch signaling pathway
Notch signaling is frequently involved in development and homeostasis in multiple tissues, resulting in diverse cellular responses, and Notch activity regulates growth, differentiation, survival, and stem cell behavior in a highly context-dependent manner[51,52]. Notch controls binary cell fate during morphogenesis, whereas YAP/TAZ translates the physical properties of the microenvironment into key cellular decisions [53]. Notch and YAP-TEAD drive the specification of trophectoderm fate downstream of cell polarity by activating the expression of the trophectoderm-specific gene Cdx2 in combination with trophectoderm-specific enhancers [54]. YAP/TAZ can act upstream of Notch signaling by activating Notch receptors[53]. For example, during postinflammatory intestinal repair, the Notch signaling pathway is downstream of YAP/TAZ activation [3]. YAP/TAZ is activated in tip cells through actomyosin tension-mediated GPCR signaling, LPA4 and LPA6 during angiogenesis. YAP/TAZ controls neovascularization by blocking β-catenin-NICD-mediated expression of the Notch ligand Dll4 [55]. In the corneal epithelium, Notch deletion triggers inflammatory cytokine secretion and continues the cycle of injury and repair [56,57]. This persistent inflammation causes ECM deposition and fibrosis, leading to activation of YAP/TAZ mechanotransduction [58]. Both in vitro and in vivo experiments have shown that low cell density or high ECM rigidity can trigger the activation of YAP/TAZ-TEAD in basal progenitor cells to maintain them via inhibiting Notch signaling[59]. In basal progenitors, the YAP/TAZ-TEAD complex activates the transcription of Dll1 and Dll3; then, cis-interaction of Dll1 and Dll3 with Notch receptors can block Notch activation, thereby preventing epidermal differentiation [59].