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Osteoblast de- and redifferentiation are controlled by a dynamic response to retinoic acid during zebrafish fin regeneration

Title data

Blum, Nicola ; Begemann, Gerrit:
Osteoblast de- and redifferentiation are controlled by a dynamic response to retinoic acid during zebrafish fin regeneration.
In: Development. Vol. 142 (1 September 2015) Issue 17 . - pp. 2894-2903.
ISSN 1477-9129
DOI: https://doi.org/10.1242/dev.120204

Abstract in another language

Zebrafish restore amputated fins by forming tissue-specific blastema cells that coordinately regenerate the lost structures. Fin amputation triggers the synthesis of several diffusible signaling factors that are required for regeneration, raising the question of how cell lineage-specific programs are protected from regenerative crosstalk between neighboring fin tissues. During fin regeneration, osteoblasts revert from a non-cycling, mature state to a cycling, preosteoblastic state to establish a pool of progenitors within the blastema. After several rounds of proliferation, preosteoblasts redifferentiate to produce new bone. Blastema formation and proliferation are driven by the continued synthesis of retinoic acid (RA). Here, we find that osteoblast dedifferentiation and redifferentiation are inhibited by RA signaling, and we uncover how the bone regenerative program is achieved against a background of massive RA synthesis. Stump osteoblasts manage to contribute to the blastema by upregulating expression of the RA-degrading enzyme cyp26b1. Redifferentiation is controlled by a presumptive gradient of RA, in which high RA levels towards the distal tip of the blastema suppress redifferentiation. We show that this might be achieved through a mechanism involving repression of Bmp signaling and promotion of Wnt/β-catenin signaling. In turn, cyp26b1(+) fibroblast-derived blastema cells in the more proximal regenerate serve as a sink to reduce RA levels, thereby allowing differentiation of neighboring preosteoblasts. Our findings reveal a mechanism explaining how the osteoblast regenerative program is protected from adverse crosstalk with neighboring fibroblasts that advances our understanding of the regulation of bone repair by RA.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Professorship Developmental Biology > Professorship Developmental Biology - Univ.-Prof. Dr. Gerrit Begemann
Profile Fields > Advanced Fields > Molecular Biosciences
Research Institutions > Research Centres > Bayreuth Center for Molecular Biosciences - BZMB
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Professorship Developmental Biology
Profile Fields
Profile Fields > Advanced Fields
Research Institutions
Research Institutions > Research Centres
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 570 Life sciences, biology
Date Deposited: 25 Jul 2017 07:10
Last Modified: 25 Jul 2017 07:10
URI: https://eref.uni-bayreuth.de/id/eprint/38869