Robin Journot 🔬| 🎾

Supported by:
@agencerecherche.bsky.social
@frm-officiel.bsky.social
@fondationarc.bsky.social
@cerclefser.bsky.social
@worldwidecancer.bsky.social
@institutcurie.bsky.social

This work was conducted at @institutcurie.bsky.social
in @frelab.bsky.social. Thank you for supporting my work over the last five years! Big thank also to Candice Merle, the first author of this story, for her help in the experimental work and to our collaborators at @lbmcinlyon.bsky.social.

Our work unifies decades of organ-specific studies into a single evo-devo framework. It argues for moving beyond organ-centric approaches toward cross-tissue comparisons to reveal conserved mechanisms of epithelial development, homeostasis, and disease.
www.biorxiv.org/content/10.1...

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.

Basal and suprabasal layers are linked by a conserved p63–Notch axis. p63 maintains basal identity and induces Notch ligands, whereas Notch signaling drives suprabasal commitment.

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.

This basal program has been repeatedly redeployed (heterotopy) in endoderm- and mesoderm-derived epithelia, allowing these tissues to initiate multilayering outside their original lineage of origin.

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

Comparative analyses across lamprey, zebrafish, xenopus, chicken, mouse, and human reveal that multilayered epithelia rely on a deeply conserved set of genes. This suggests that the molecular foundations of epithelial stratification were established early in vertebrate evolution.

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...

Supported by:
@agencerecherche.bsky.social
@frm-officiel.bsky.social
@fondationarc.bsky.social
@cerclefser.bsky.social
@worldwidecancer.bsky.social
@institutcurie.bsky.social

Cell-type-specific nucleotide sharing through gap junctions impacts sensitivity to replication stress in Drosophila Boumard et al. demonstrate gap-junction-dependent tissue-scale nucleotide sharing, which impacts cellular sensitivity to perturbation of nucleotide homeostasis and replication stress. Drosophila wing ...

The PhD work of @bboumard.bsky.social officially out in print! Happy to share this issue with our downstairs colleagues in the BDD @frelab.bsky.social @robinjournot.bsky.social

www.cell.com/developmenta...

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...

Dissecting the impact of transcription factor dose on cell reprogramming heterogeneity using scTF-seq - Nature Genetics This study introduces single-cell transcription factor (TF) sequencing, a single-cell barcoded and doxycycline-inducible TF overexpression approach that reveals dose-sensitive functional classes of TFs and cellular heterogeneity by mapping TF dose-dependent transcriptomic changes during the reprogramming of mouse embryonic multipotent stromal cells.

🧵1/ Excited to share our new paper introducing a new #singlecell assay: scTF-seq, a high-throughput single-cell approach to explore how transcription factor (TF) dose shapes cell identity and reprogramming outcomes. 🔗 www.nature.com/articles/s41... Big congrats to the entire team @EPFL & @SIAT_China

"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

From a FACS-contaminating cell population to a multi-organ project — learn the Behind the Story of our work on conserved signals in epithelial organogenesis 👉 www.sciencedirect.com/science/arti...

Yes! We think this mechanism goes way beyond glands. We're now exploring a broader range of tissues, stay tuned for what's coming next!

Great question! We haven’t inferred or directly measured mechanical forces yet, but in a follow-up project we’re actively investigating the mechanical component of the symmetry-breaking event. Very curious to see how it ties into YAP localization and happy to discuss more!

Students (Master's/PhD), do not miss this fantastic Developmental Biology course of @sorbonne-universite.fr and @institutcurie.bsky.social - It is FREE and open to international students, however, room and board + travel are not included.

training.institut-curie.org/courses/deve...

This work was funded by @institutcurie.bsky.social, ‪‪‪@cnrsbiologie.bsky.social, @psl-univ.bsky.social, @agencerecherche.bsky.social , @frm-officiel.bsky.social, @cerclefser.bsky.social, @fondationarc.bsky.social and @worldwidecancer.bsky.social.

Full publication in @cp-devcell.bsky.social : authors.elsevier.com/c/1lM285Sx5g...

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.

In regeneration, we saw the same transitional state: YAP⁺p63⁺HES1⁺.
→ Developmental programs are reused for repair.

YAP acts then as a capacitor, counting the number of cell within the tissue before allowing cells to differentiate.

We found the key: YAP.
Initially nuclear in all cells, it becomes cytoplasmic in internal cells—coinciding with symmetry breaking and fate commitment. When we forced YAP activity, organoids didn’t break symmetry—cells stayed in a stem-like state, co-expressing p63 & HES1.
Same results in embryos!

But why do organoids stay homogeneous until ~13 cells?
Theoretical models say symmetry can break in 2 cells.
Here, an active mechanism seems to delay fate decisions early on.

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.

We observed that fate segregation (K5 outside, K8 inside) happened not over time, but when organoids reached 13–21 cells.
→ This suggests size-dependent symmetry breaking drives fate commitment.