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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 heatshocks, 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 wild-type 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 wild-type 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).