The Goldman lab publishes a research article in eLife

Retinal injury in adult zebrafish suppresses tgfb3 RNA expression at the injury site (*), and this suppression precedes MG proliferation that begins ~2 days post-injury (dpi). In situ hybridization detects tgfb3 RNA (blue/purple), BrdU immunofluorescence identifies proliferating cells (red/orange), and the size marker is 40 microns.

Unlike mammals, zebrafish have a remarkable ability to regenerate retinal neurons that were lost due to injury or disease. Neuronal degeneration in the zebrafish retina stimulates Müller glia (MG) to proliferate and generate multipotent progenitors for retinal repair. Previous studies reported that retinal injury stimulates pSmad3 signaling in injury-responsive MG. Contrary to these findings, researchers in the Goldman lab report that pSmad3 expression is restricted to quiescent MG and suppressed in injury-responsive MG. Their data indicate that Tgfb3 is the ligand responsible for regulating pSmad3 expression. Remarkably, although overexpression of either Tgfb1b or Tgfb3 can stimulate pSmad3 expression in the injured retina, only Tgfb3 inhibits injury-dependent MG proliferation, suggesting the involvement of a non-canonical Tgfb signaling pathway. Furthermore, inhibition of Alk5, PP2A, or Notch signaling rescues MG proliferation in zebrafish overexpressing Tgfb3. The observation that this Tgfb3 signaling pathway is active in zebrafish MG but undetectable in mouse MG suggests that it may contribute to the different regenerative capabilities of MG from fish and mammals.

Read the eLife article HERE.