Taken together, multilayered epithelia development follows a spatial and evolutionary hourglass: basal layers reactivate an ancestral ectodermal program, while suprabasal compartments diversify through modular, lineage-specific innovations.

Lineage-tracing experiments across all 14 tissues show that activating Notch in basal cells consistently triggers suprabasal commitment, confirming the universality of this regulatory connection in stratified tissues.

In contrast, suprabasal compartments show strong enrichment for tissue-specific and architecture-specific transcriptional modules. Functional diversification emerges primarily in suprabasal layers and follow a Russian-doll organization.

We find that this conserved GRN is evolutionarily compartmentalized. Basal cells consistently deploy an ancestral ectodermal regulatory module centered on p63.

Multilayered epithelia emerge from ectoderm, endoderm, and mesoderm, yet all adopt the same basic architecture: a basal compartment supporting one or more differentiated suprabasal layers. Do these different organs use distinct mechanisms, or a shared regulatory program?

🚨 New preprint!
We built a single-cell atlas of 14 multilayered epithelia and revealed a conserved transcriptomic program guiding tissue architecture and fate composition. Our work brings decades of tissue-specific studies together into a unified evo-devo framework.
www.biorxiv.org/content/10.1...

Our paper is on the cover of @cp-devcell.bsky.social . Image: embryonic murine salivary-gland explants stained for fate determinants; p63 (cyan) and HES1 (yellow). Thanks to everyone involved.
doi.org/10.1016/j.de...

"Contractile fibroblasts form a transient niche for the branching mammary epithelium."
Now out: rdcu.be/eIIKD
A great contribution from Jakub Sumbal, showing how stromal cells, and diverse fibroblast subsets, regulate branching morphogenesis.
@sumbalovakoledova.bsky.social @frelab.bsky.social

Despite distinct germ layer origins and divergent adult functions, all 4 glands rely on the same YAP–Notch–p63 circuit to specify fate and pattern.
We propose an updated hourglass model where this conserved module acts as a developmental bottleneck in organogenesis.

We then asked: what regulates this decision?
Notch activation (in vivo or organoids) forced luminal fate.
Notch inhibition blocked it.
→ Notch is a gatekeeper of luminal identity.
We further demonstrated that symmetry breaking appeared through lateral inhibition.

🧵Just out !
We reveal how 4 branched epithelia—mammary, lacrimal, salivary & prostate—use a conserved YAP–Notch–p63 circuit to self-organize during development & regeneration.
Here’s the story👇
authors.elsevier.com/c/1lM285Sx5g...
Work done in @frelab.bsky.social at ‪
‪ @institutcurie.bsky.social

A new platform, a new post!
Our #Stemcell #DevBio and #Regeneration
story by Silvia Fre's lab at InstitutCurie is on biorXiv.
Link: tinyurl.com/2uspcd3u

We reveal how 4 epithelia self-organize during embryonic development and regeneration.