PgmNr Z612: Wnt signaling is required for adult zebrafish kidney regeneration.

Authors:
C. N. Kamei 1 ; Y. Liu 1 ; N. A. Hukriede 2 ; I. A. Drummond 1,3


Institutes
1) Massachusetts General Hospital, Charlestown, MA; 2) University of Pittsburgh, Pittsburgh, PA; 3) Harvard Medical School, Boston, MA.


Abstract:

Kidney regeneration in zebrafish occurs by repair of existing nephrons as well as by de novo generation of new nephrons from adult organ progenitor cells by neonephrogenesis. We report here that Wnt signaling plays an essential role in adult zebrafish kidney regeneration. Newly forming nephron condensates in the developing mesonephros as well as those formed in the adult in response to gentamicin injury express the Wnt receptor frizzled 9b (fzd9b) and the canonical Wnt target gene lef1. In the Tg(lhx1a:GFP) nephron progenitor reporter line, both individual lhx1a-positive adult kidney progenitor cells and nephron condensates are specifically marked by expression of fzd9b. Canonical Wnt signaling reporter line Tg(TCF/Lef-miniP:dGFP) combined with EdU labeling shows distinct zones of hi vs low Wnt activity and proliferation in new nephron formation. Pharmacological blockade of Wnt signaling using IWR1 and IWP2 led to a decrease in lhx1a+ nephron condensates after injury. EdU labeling in Tg(lhx1a:GFP) fish after gentamicin injury reveals that newly forming condensates are actively proliferating and this proliferation is blocked by Wnt inhibition. wnt9b is strongly induced in collecting duct epithelia after injury, making it a strong candidate for a mediator of the regeneration response. Our results demonstrate an essential role for Wnt signaling in adult zebrafish kidney regeneration. Identification of fzd9b as a new marker of adult kidney progenitor cells opens new avenues to investigate their developmental origins and regenerative potential.



ZFIN Genetics Index
1. lhx1a
2. fzd9b
3. lef1
4. wnt9b