Denis Krndija

Mechanical forces shape the developing brain 🧠💥 Compression from high cell density doesn’t just squeeze cells - it compromises mitotic fidelity! New preprint on how mechanics impact neural development from Veronique Marthiens & co-authors @institutcurie.bsky.social @cbitoulouse.bsky.social
🧠🔧👇

Well done Robin and @frelab.bsky.social on this beautiful story - it’s great to see it published!! Bravo 👏 🍾 🥳

🧵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

My first experience at a GRC- excellent talks & stimulating conversations. Thanks to everyone to who stopped by my poster- your feedback were incredibly valuable to me. And of course, infinite gratitude goes to @yap-lab.bsky.social, an exceptional mentor and support throughout my journey!

Woohoo!! Congrats @julianeg.bsky.social !!! 🍾 🥳

A highlight of our recent story!

Thanks for your insights, Marija! 🙌 🥰
We're excited to explore how mechanical forces shape physiological complexity between distinct epithelial cell types in vivo. And yes - tricellular junctions reinforce under compression, but often crack first… and kick off the further fracturing process! 💥

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...

Enjoying great science and stunning alpine views at the GRC on Cell Contact & Adhesion in Les Diablerets 🇨🇭⛰️ Proud of our PhD students Dhriti and Vishnu for their terrific work - posters and talks full of exciting insights! #CellContactAndAdhesionGRC #CellBiology #PhDLife #LesDiablerets

Well done Sulov and all the authors!! 🙌 👏

Program and application instructions for the 2025 Mechanobiology of tissue morphogenesis and disease workshop in Baeza, Spain, October 21-23. Apply at https://www.unia.es/estudios-y-acceso/oferta-academica/formacion-continua/workshop-mechanobiology-of-tissue-morphogenesis-and-disease

Interested in Developmental Mechanics??? We are organizing a mechanobiology workshop in Baeza, Spain, October 21-23, 2025. Come join us (and please help us spread the word)!!!

Thanks a lot @bensimonbrito.bsky.social ! 🙏

Thank you @naturemethods.bsky.social for highlighting our recent paper on "Spatial Mechano-Transcriptomics" in your April Issue:
www.nature.com/articles/s41...

www.nature.com/articles/s41...

We are excited to share our recent preprint on how tissue spreading guides extracellular matrix changes during early morphogenesis @gurdoninstitute.bsky.social

Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell Bhattacharya et al. delineate chromatin and mRNA dynamics of intestinal secretory differentiation. They demonstrate that goblet and Paneth cells are phenotypic variants of a facile signal-responsive A...

I am excited to share my latest Postdoctoral work @cp-cellstemcell.bsky.social @cellpress.bsky.social (dlvr.it/TK2Fzl), in which we reveal that goblet and Paneth cells aren’t fixed lineages but represent dynamic states influenced by local cues. Here's a walkthrough of what we found (🧵)....

Thanks a lot Adrien, that's very kind of you!!

Hi! 👋 It’s a “standard” 3D gut organoid on a coverslip, in a Matrigel dome. Email me if you need any help with these!

Stretch-induced endogenous electric fields drive directed collective cell migration in vivo - Nature Materials Electric fields guide collective cell migration in developing embryos of Xenopus laevis via a voltage-sensitive phosphatase.

REPOSTING this here just to officially leave "the other place"

Our work on the role of endogenous electric fields in guiding collective cell migration during #morphogenesis is out @naturematerials.bsky.social
nature.com/articles/s41...

Well done Elias & the team!!! 🎉

📩 Let us know what you think about our first “baby”!
We are thankful to the amazing @cbitoulouse.bsky.social animal & imaging platforms, critical input from our colleagues and funding from @cnrs.fr, @agencerecherche.bsky.social, and @frm-officiel.bsky.social - we raise our Goblets to you! 🥂 🙏 😉

⚠️ However, exacerbated fracturing under goblet hypertrophy could become dangerous: as the tissue becomes more fragile, additional mechanical challenges (plentiful in the gut) may trigger deeper cracks and tissue disintegration – potentially setting the stage for inflammatory disease

Since we observed GAFs in embryonic gut epithelium (before peristalsis, microbiota, and immune system), we propose that GAFs act as mechanical buffers, absorbing stress & alleviating strain at the goblet-enterocyte interface, as a way to potentially increase epithelial resiliance to strain! 💪

Could there be a possible role for these GAFs? 🧐
Epithelial cracks can serve functional roles in development & tissue mechanics, as shown in blastocyst hydraulic fracturing, stretch-induced cracks in epithelial monolayers, or placozoan fractures induced by migration stress...

Goblet cells mechanically breach the epithelial barrier in gut homeostasis The intestinal epithelium has to maintain a tight barrier to the harsh luminal environment. The absorptive enterocytes have a polygonal and columnar shape, while mucus-producing goblet cells have a ro...

🔗 Preprint link: www.biorxiv.org/content/10.1...
#mechanobiology #intestinalepithelium #gobletcells #biomechanics #organoids #gutbarrier

Take-home message 📌:
The gut epithelium is shaped by mechanical forces at the single-cell level: Goblet cells exert compressive forces on their neighbours, driving fractures that breach the barrier depending on the neighbors’ fluidity - a mechanical interplay with physiological relevance! 🚨 (9/9)

We tested our model predictions by modulating tissue rigidity via myosin II in vivo (NMIIA-KO) and in 2D organoids – tissue fluidification reduced GAFs, even under goblet cell hypertrophy! → It’s the balance between goblet pressure and tissue fluidity that controls junctional integrity! (8/9)

To understand the force balance behind rupture, we teamed up with Shi-Lei Xue 🖥️ (another new PI!👋). Through an innovative vertex model incorporating fractures, we identified 2 key GAF parameters:
1) Goblet size/pressure → bigger goblets = more GAFs
2) Tissue fluidity → more fluid = fewer GAFs! (7/9)

Are GAFs linked to food transit or microbiota? 🤔 Surprisingly, GAFs exist in embryonic intestine (E16.5), where the lumen is empty & neither microbiota nor immune cells are present! Plus, we reproduced GAFs in 2D organoids, confirming their epithelium-autonomous nature! 💡 (6/9)

What about the extrinsic mechanical stresses in the gut? Goblet hypertrophy not only increases GAF size & number but also fracture depth (reaching desmosomes), weakening the epithelium’s resistance to luminal shear stress. This escalated into large-scale epithelial cracking in our exp.! 💥💥💥 🤯 (5/9)

Are enterocytes just passive observers?
No! They accumulate E-cadherin & other junctional proteins in a mechano-sensitive response to goblet-induced strain! Yet, goblet hypertrophy overcomes this active response, leading to full junctional failure in a tight > adherens > desmosome hierarchy! ⚠️ (4/9)