Editors' ChoiceRegeneration

Maintaining Organ Integrity

Science Signaling  02 Sep 2008:
Vol. 1, Issue 35, pp. ec310
DOI: 10.1126/scisignal.135ec310

Facultative regeneration is the process by which an amputated or otherwise injured organ is reformed, and homeostatic regeneration is the process that maintains a tissue under normal conditions. An organ’s capacity to regenerate following amputation is positively correlated with the amount of cell turnover in that organ, which suggests that the processes share some molecular components. However, it was not necessarily expected that they would be directed by the same signaling pathways, given that one process is activated by trauma and the other is constitutive. Wills et al. tested whether the requirement for fibroblast growth factor (FGF) signaling in facultative regeneration also extended to homeostasis in zebrafish fins. When they reduced FGF signaling by daily expression of a dominant-negative form of FGF receptor 1 from a heat shock-inducible promoter, the animals showed a progressive loss of distal fin tissue, having shortened fins with ragged edges after 60 days. When the heat shock regimen was abandoned, the fish reestablished normal fin morphology within 30 days. Similar fin atrophy occurred in animals lacking Fgf20a, an FGF ligand specifically required for facultative regeneration. Rates of proliferation and apoptosis indicated that cell turnover was higher in distal than in proximal fin tissues, and several molecular markers of facultative regeneration, including fgf20a, were constitutively expressed in uninjured wild-type distal fin tissues. The authors propose that a small amount of constitutive FGF signaling in the distal portions of fins promotes an amount of proliferation sufficient to counterbalance the high cell turnover rate to maintain homeostasis.

A. A. Wills, A. R. Kidd III, A. Lepilina, K. D. Poss, Fgfs control homeostatic regeneration in adult zebrafish fins. Development 135, 3063-3070 (2008). [Abstract] [Full Text]