iiinova — where your digital self keeps evolving

Alessandro De Simone @desimonelab.bsky.social · 18/09/2026

Thank you Hahn! We are happy as well :)

Alessandro De Simone @desimonelab.bsky.social · 18/09/2026

Hi Ben, thank you! This is an intriguing question, we do not know yet and its scaling properties make it particularly mysterious. We wonder if cell density or the stiffness of the bone matrix are involved.

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Alessandro De Simone @desimonelab.bsky.social · 17/09/2026

Congratulations to Konrad Marx, who is leading this work, and our collaborators Simone Cicolini and Guillaume Salbreux, as well as Coline Coudeville. Shut out to the enormous work of Delphine Colevret!

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Alessandro De Simone @desimonelab.bsky.social · 17/09/2026

A simple model including a moving front, with the measured properties, separating a proliferating region from a non-proliferating region, plus a basal level of cell death, can explain the observed osteoblast number dynamics and its amplification factor.

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Alessandro De Simone @desimonelab.bsky.social · 17/09/2026

The position of the maturation front scales with tissue size across different scales. “Scaling scales”, we are sorry, but the pun in unavoidable at the moment. The front arrives at the end of the tissue at the same time regarless of its size.

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Alessandro De Simone @desimonelab.bsky.social · 17/09/2026

Live imaging of new and existing biosensor/reporter lines shows that bone maturation coincides with reduced expression of the fibroblast growth factor receptor 3 (fgfr3) and with lower Erk and p38 activity.

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Alessandro De Simone @desimonelab.bsky.social · 17/09/2026

The maturation front is slightly preceded by deposition of mineralized bone matrix (grey).

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Alessandro De Simone @desimonelab.bsky.social · 17/09/2026

Combining live imaging and transcriptomics, we found a moving front of osteoblast maturation that progressively travels across the tissue. Osteoblasts start out immature and proliferative (green), then mature into hypertrophic non-dividing cells (yellow). Dpp: days post-plucking.

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Alessandro De Simone @desimonelab.bsky.social · 17/09/2026

First, we show that regeneration accurately recovers scales to their original pre-injury size. This is achieved by controlling the initial size of the regenerating scale, then amplifying osteoblast number by a fixed factor over a set time. How is this proliferation control achieved?

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Alessandro De Simone @desimonelab.bsky.social · 17/09/2026

How is proliferation modulated in regeneration for tissues to reach their right size? We found that, in zebrafish scales, proliferation is shut down by a moving front of osteoblast maturation. The front's dynamics scale with tissue size, ensuring proper osteoblast amplification. tinyurl.com/5e45twx3

tinyurl.com

A moving front of osteoblast maturation scales regenerating zebrafish bone

Successful regeneration recovers lost tissues to their original form. Here, we investigate how proliferation of bone-forming osteoblasts is timely regulated to control tissue size during zebrafish sca...

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Reposted by Alessandro De Simone

The Milinkovitch-Tzika lab @lanevol.bsky.social · 08/05/2026

Charles Darwin comes back to life to wish Sir David Attenborough a happy 100th birthday. Our 3.5-min film from the LANE (University of Geneva) celebrates "the man who helped the world fall in love with nature". Happy #AttenboroughDay ! #bbc @biology-unige.bsky.social

youtu.be

An extraordinary guest to celebrate Sir David Attenborough

YouTube video by The LANE channel

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Alessandro De Simone @desimonelab.bsky.social · 16/12/2025

Tristan Guyomar and I wrote a review on physical mechanisms coordinating regeneration - Featured: signalling/mechanical gradients, travelling waves and nematic fields - Dramatis personae: axolotls, hydra, planaria, spiny mice and zebrafish (ofc) with a jellyfish cameo tinyurl.com/3upzrdbs

tinyurl.com

Gradients, waves and nematics: quantitative perspectives on regeneration

Regeneration restores a damaged body part to its original size, shape and structure. Research over the last decades identified signaling pathways, cel…

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Alessandro De Simone @desimonelab.bsky.social · 21/11/2025

Ben! Thank you 😀 There is no day we are not grateful for your lines, protocols and discoveries!

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Alessandro De Simone @desimonelab.bsky.social · 21/11/2025

Thank you, Stefano! And thank you for your continuing support :)

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Alessandro De Simone @desimonelab.bsky.social · 21/11/2025

Thank you! I fully agree with you, this is an advantage of slow waves 😀

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

Special thanks to Prof. Franka Voigt for this great collaboration - without who this project would have not been possible. Btw, a collaboration born at #SY-STEM 2023 in Vienna quite serendipitously.

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

Congratulations to Coline, Tristan, and all people involved, on this important step!

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

This suggests a fascinating paradigm for the control of tissue regeneration: the more Erk waves sweep across the tissue, the more the tissue matures, potentially regulating future waves to tune overall growth.

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

These results reveal a self-regulating and spatially organized signaling circuit in which Erk activity waves shape their own inhibition landscape as they propagate, while simultaneously driving tissue maturation.

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

We continued our analysis by asking if Erk waves regulate other aspects of osteoblast regeneration. We discovered that Erk waves modulate the transcription of the bone maturation transcription factor osterix, which is activated in trailing transcriptional waves.

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

ReLUs are classic processing units of neural networks and allow proportional responses to strong stimuli, while buffering noise.

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

We found that the abundance of inhibitor transcripts depends on Erk activity through Rectified Linear Unit (ReLU) responses: transcript levels increase linearly with Erk activity once a threshold is crossed.

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

To understand how refractory periods arise, we analyzed transcriptional patterns. Together with the Voigt lab at UZH, we developed an smFISH technique for whole-mount scales. This revealed that Erk waves induce beautiful trailing waves of the inhibitor transcripts dusp5, spry2, and spry4.

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

We further noticed that, when two waves meet, they merge, which suggests that waves are followed by regions that are refractory to Erk activation. This refractory region is predicted to result from high concentrations of Erk inhibitors, induced by Erk itself.

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

Erk waves were proposed to result from an excitable system including interactions with Erk activators and inhibitors. Compatibly with excitable Erk waves theory, we observed that Erk waves can form striking spiral patterns in scales.

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

Erk inhibitors are predicted to tune wave frequency, which controls tissue growth.

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Alessandro De Simone @desimonelab.bsky.social · 20/11/2025

The lab’s first pre-print! We investigated how growth-inducing Erk activity waves are regulated in regenerating zebrafish scales. We discovered that Erk waves are followed by waves of expression of their own inhibitors, as predicted by excitable waves theory. tinyurl.com/26r2cmpj

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Reposted by Alessandro De Simone

Zebrafish Rock! 🎃 @zebrafishrock.bsky.social · 20/11/2025

New work from @desimonelab.bsky.social lab 🌊🐟

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Reposted by Alessandro De Simone

Practical Course on Developmental Biology QUINTAY @devbioquintay.bsky.social · 11/12/2024

We have moved to this new location as we prepare to launch a new edition of the Practical Course on Developmental Biology, Quintya-2025. This course began more than 25 years ago, and we are excited to bring together an excellent lineup of faculty and students for this latest edition

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