Journal
CURRENT BIOLOGY
Volume 26, Issue 22, Pages 2981-2991Publisher
CELL PRESS
DOI: 10.1016/j.cub.2016.08.072
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Funding
- National Science Foundation [1106401]
- Whitehead Faculty Scholar Award
- NIH [R01 GM074057]
- [RBAP11BYNP-Newton]
- Direct For Education and Human Resources
- Division Of Graduate Education [1106401] Funding Source: National Science Foundation
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The blastema is a mass of progenitor cells that enables regeneration of amputated salamander limbs or fish fins. Methodology to label and track blastemal cell progeny has been deficient, restricting our understanding of appendage regeneration. Here, we created a system for clonal analysis and quantitative imaging of hundreds of blastemal cells and their respective progeny in living adult zebrafish undergoing fin regeneration. Amputation stimulates resident cells within a limited recruitment zone to reset proximodistal (PD) positional information and assemble the blastema. Within the newly formed blastema, the spatial coordinates of connective tissue progenitors are predictive of their ultimate contributions to regenerated skeletal structures, indicating early development of an approximate PD pre-pattern. Calcineurin regulates size recovery by controlling the average number of progeny divisions without disrupting this pre-pattern. Our longitudinal clonal analyses of regenerating zebrafish fins provide evidence that connective tissue progenitors are rapidly organized into a scalable blueprint of lost structures.
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