A moving front of osteoblast maturation scales regenerating zebrafish bone
- 1University of Geneva
Abstract
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 scale regeneration. Regeneration of the scale osteoblast tissue proceeds in two phases: an initial osteoblast proliferative expansion followed by hypertrophic growth without cell division. First, we show that regeneration recovers scale size by amplifying the number of osteoblasts by a fixed factor, starting from a properly scaled tissue primordium. This fixed expansion is achieved by regulating proliferation such that osteoblast number increases roughly linearly, with the rate of increase scaling with initial osteoblast number, and halting cell proliferation at a given time. To understand the mechanisms underlying this proliferation control, we used live imaging of transgenic reporters and biosensors together with transcriptomics. We uncover that proliferation arrest is imparted by a moving front of osteoblast maturation travelling outward across the scale, with dynamics that scales with tissue size. The osteoblast maturation front coincides with onset of hypertrophy and bone deposition, and it is accompanied by reduction in expression of the fibroblast growth factor receptor 3 (fgfr3) and activity of the kinases Erk (Extracellular signal-Regulated Kinase) and p38. Inhibition of Fgf/Erk signaling and osteoblast proliferation does not alter the progression of the maturation front. We show that the scaling maturation front can quantitatively explain the osteoblast proliferation dynamics and its scaling across different tissue sizes. Overall, we identify a moving front of cell maturation as a mechanism for controlling cell proliferation across a regenerating tissue.
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BibTeX
@misc{marx2026moving,
title = {{A moving front of osteoblast maturation scales regenerating zebrafish bone}},
author = {K. Marx and S. Cicolini and D. Colevret and C. Coudeville and G. Salbreux and A. De Simone},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.745769},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.745769v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A moving front of osteoblast maturation scales regenerating zebrafish bone
AU - K. Marx
AU - S. Cicolini
AU - D. Colevret
AU - C. Coudeville
AU - G. Salbreux
AU - A. De Simone
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.745769
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.745769v1
AB - 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 scale regeneration. Regeneration of the scale osteoblast tissue proceeds in two phases: an initial osteoblast proliferative expansion followed by hypertrophic growth without cell division. First, we show that regeneration recovers scale size by amplifying the number of osteoblasts by a fixed factor, starting from a properly scaled tissue primordium. This fixed expansion is achieved by regulating proliferation such that osteoblast number increases roughly linearly, with the rate of increase scaling with initial osteoblast number, and halting cell proliferation at a given time. To understand the mechanisms underlying this proliferation control, we used live imaging of transgenic reporters and biosensors together with transcriptomics. We uncover that proliferation arrest is imparted by a moving front of osteoblast maturation travelling outward across the scale, with dynamics that scales with tissue size. The osteoblast maturation front coincides with onset of hypertrophy and bone deposition, and it is accompanied by reduction in expression of the fibroblast growth factor receptor 3 (fgfr3) and activity of the kinases Erk (Extracellular signal-Regulated Kinase) and p38. Inhibition of Fgf/Erk signaling and osteoblast proliferation does not alter the progression of the maturation front. We show that the scaling maturation front can quantitatively explain the osteoblast proliferation dynamics and its scaling across different tissue sizes. Overall, we identify a moving front of cell maturation as a mechanism for controlling cell proliferation across a regenerating tissue.
ER -