PT  - JOURNAL ARTICLE
AU  - Scott Stewart
AU  - Gabriel A. Yette
AU  - Heather K. Le Bleu
AU  - Astra L. Henner
AU  - Joshua A. Braunstein
AU  - Jad W. Chehab
AU  - Michael J. Harms
AU  - Kryn Stankunas
TI  - Skeletal geometry and niche transitions restore organ size and shape during zebrafish fin regeneration
AID  - 10.1101/606970
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 606970
4099  - http://biorxiv.org/content/early/2019/07/25/606970.short
4100  - http://biorxiv.org/content/early/2019/07/25/606970.full
AB  - Regenerating fish fins return to their original size and shape regardless of the nature or extent of injury. Prevailing models for this longstanding mystery of appendage regeneration speculate fin cells maintain uncharacterized positional identities that instruct outgrowth after injury. Using zebrafish, we show differential Wnt production by pools of progenitor-maintaining niche cells promotes the correct extent of regeneration across the fin. We identify Dachshund transcription factors as niche markers and show the niche derives from mesenchyme populating cylindrical and progressively tapered fin rays. The niche, and consequently Wnt, steadily dissipates as regeneration proceeds; once exhausted, ray and fin growth stops. Supported by mathematical modeling, we show longfint2 zebrafish regenerate exceptionally long fins due to a broken niche “countdown timer”. We conclude regenerated fin size is dictated by the amount of niche formed upon damage – which is simply dependent on the availability of intra-ray mesenchyme defined by skeletal girth at the injury site. This “transpositional scaling” model contends mesenchyme-niche state transitions and self-restoring skeletal geometry rather than cell memories determine a regenerated fin’s size and shape.