Alessandro De Simone
desimonelab.bsky.social
Alessandro De Simone
@desimonelab.bsky.social
Physical principles of regeneration in zebrafish. Assist. Prof. @Genevunige. Passionate of zebrafish scales, bone morphogenesis and signalling dynamics. #SciComm and Improv theatre. https://tinyurl.com/23str3yn
Thank you Hahn! We are happy as well :)
September 18, 2026 at 10:03 AM
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.
September 18, 2026 at 10:03 AM
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!
September 17, 2026 at 5:33 PM
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.
September 17, 2026 at 5:33 PM
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.
September 17, 2026 at 5:33 PM
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.
September 17, 2026 at 5:33 PM
The maturation front is slightly preceded by deposition of mineralized bone matrix (grey).
September 17, 2026 at 5:33 PM
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.
September 17, 2026 at 5:33 PM
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?
September 17, 2026 at 5:33 PM
Ben! Thank you 😀 There is no day we are not grateful for your lines, protocols and discoveries!
November 21, 2025 at 9:56 AM
Thank you, Stefano! And thank you for your continuing support :)
November 21, 2025 at 9:42 AM
Thank you! I fully agree with you, this is an advantage of slow waves 😀
November 21, 2025 at 9:37 AM
Thank you so much!
November 21, 2025 at 9:35 AM
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.
November 20, 2025 at 9:28 PM
Congratulations to Coline, Tristan, and all people involved, on this important step!
November 20, 2025 at 6:11 PM
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.
November 20, 2025 at 6:11 PM
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.
November 20, 2025 at 6:11 PM
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.
November 20, 2025 at 6:11 PM
ReLUs are classic processing units of neural networks and allow proportional responses to strong stimuli, while buffering noise.
November 20, 2025 at 6:11 PM
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.
November 20, 2025 at 6:11 PM
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.
November 20, 2025 at 6:11 PM
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.
November 20, 2025 at 6:11 PM