Abstract:
Understanding the intricate mechanisms governing epidermal pattern formation, particularly
within ectodermal appendages like hair follicles, is a key pursuit in developmental biology.
Reciprocal interactions between mesenchymal and epithelial cells regulate hair follicle
growth and development through various signaling pathways, yet the underlying molecular
pathways remain elusive. Our investigation focuses on Thy1, a cell surface protein tethered
via a glycosylphosphatidylinositol (GPI) anchor, which plays a multifaceted role in cell-cell
and cell-matrix adhesion. We found that Thy1 significantly influences hair follicle
development through the YAP (Yes-associated protein) mediated signaling pathway. In-vivo
deletion experiments revealed a marked increase in hair follicle numbers upon Thy1
deletion, attributable to the activation of the YAP/Integrin-β1/Src module. Additionally,
employing ultrasound-guided lentiviral delivery and pharmacological inhibition, we elucidated
the pronounced regulatory role of YAP in hair follicle morphogenesis, further delineating the
Thy1-dependent phenotypes. Our findings underscore the pivotal role of YAP activity in
regulating hair follicle development, shedding light on potential therapeutic implications for
hair-related disorders and presenting exciting prospects in the realm of regenerative
medicine applications.
