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Conserved signals dictate symmetry braking and regeneration of multilayered epithelia

Organogenesis is a highly intricate and tightly regulated process that is essential for the formation of functional organs during embryonic development. Epithelial tissues are crucial for shaping organs during development and for maintaining tissue integrity in adulthood. Organ development requires a tight coordination between stem cell differentiation and tissue morphogenesis, but there is still a lot to learn about how these processes are dynamically orchestrated in vivo to give rise to functional tissues with the correct shape and cell type allocation, especially in complex branched tissues.

During my talk, I will present our recent work on how Notch signaling plays a crucial role for establishing cell fate commitment in development and maintaining lineage plasticity in adult epithelial cells from various mouse multilayered epithelia. We identified a self-organizing mechanism in which positional cues regulate the activity of YAP, p63, and Notch, thereby guiding stem cell fate in the mammary, lacrimal, salivary, and prostate glands, both during development and in regenerative contexts. 

We then established a transcriptomic atlas of 14 stratified epithelia from different embryonic origin, which we combined with in vitro and in vivo Notch perturbations. This approach revealed the evolutionary origin and conserved functions of Notch and p63 in epithelial stratification processes. 

Together, this project uncovers fundamental principles governing epithelial organogenesis and demonstrate that, despite arising from distinct embryonic germ layers, these tissues are subject to a shared set of conserved developmental constraints that guide their final architecture and organization.