In zebrafish, Müller glia function as intrinsic retinal stem cells that can regenerate ablated
neurons. Understanding the mechanisms governing neuronal stem cells may provide clues
to regenerate neurons in mammals. We report that in Müller glia the cytokine/growth factor,
Midkine-a, functions as a core autocrine regulator of the cell cycle. Utilizing midkine-a
mutants, we determined that Midkine-a regulates elements of an Id2a-retinoblastoma
network in reprogrammed Müller glia that controls the expression of cell cycle genes and is …

In the retina of zebrafish, Müller glia have the ability to reprogram into stem cells capable of
regenerating all classes of retinal neurons and restoring visual function. Understanding the
cellular and molecular mechanisms controlling the stem cell properties of Müller glia in
zebrafish may provide cues to unlock the regenerative potential in the mammalian nervous
system. Midkine is a cytokine/growth factor with multiple roles in neural development, tissue
repair, and disease. In midkine-a loss-of-function mutants of both sexes, Müller glia initiate …