Fig. 4. Homeostatic responses of cell proliferation and gene expression in zebrafish fins.

(A) A model for “priming” homeostatic regeneration through manipulation of Fgf signaling. If developmental gene expression and cell proliferation are homeostatic events that rely on Fgf signaling, then these events should increase in intensity as a response after fins recover from a period of Fgfr inhibition. (B) BrdU incorporation in uninjured fins after a priming protocol of 14 days of daily heat-shocks, and 5 days at room temperature (14d hs/5 dr). This protocol was predicted to repress, and then release and increase, homeostatic proliferation in hsp70:dn-fgfr1 fins. Transgenic fins display a burst of BrdU incorporation in distal fin tissue during recovery (brackets) that is not detectable in wildtype fins. One lobe of the caudal fin is shown. (C) Expression of regeneration marker genes increases during recovery of Fgf signaling. mkp3 and msxb are robustly expressed in regenerating fins (4 dpa, arrowheads), but expression in the uninjured fin or primed wildtype fin is undetectable by whole mount in situ hybridization. However, mkp3 and msxb levels increase visibly following homeostatic priming of the fin by transient Fgfr inhibition (arrowheads).