Spatiotemporal Gradient of Mesenchymal Stiffness Controls Sweat Gland Morphogenesis

The study investigates how gradients of tissue stiffness influence sweat gland morphogenesis, focusing on the role of mechanical and biochemical signals. By manipulating tissue stiffness during development, researchers found that the mechanosensitive channel Piezo1 translates these cues into a Wnt5a gradient, which directs epithelial progenitor cells towards either ductal elongation or glandular differentiation. Deleting Wnt5a, Piezo1, or Collagen 1a1 in the dermis disrupted ductal length and gland size. A microfluidic device was developed to mimic these conditions, confirming that Wnt signaling levels dictate the transition from ductal to glandular fate. These findings highlight the interplay between the mesenchymal microenvironment and glandular progenitors, offering insights for glandular epithelium regeneration.