RT Journal Article
SR Electronic
T1 Midkine-a functions as a universal regulator of proliferation during epimorphic regeneration in adult zebrafish
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.14.040972
DO 10.1101/2020.04.14.040972
A1 Nicholas  B Ang
A1 Alfonso Saera-Vila
A1 Caroline Walsh
A1 Peter  F Hitchcock
A1 Alon Kahana
A1 Ryan Thummel
A1 Mikiko Nagashima
YR 2020
UL http://biorxiv.org/content/early/2020/04/14/2020.04.14.040972.abstract
AB Zebrafish have the ability to regenerate damaged cells and tissues by activating quiescent stem and progenitor cells or reprogramming differentiated cells into regeneration-competent precursors. Proliferation among the cells that will functionally restore injured tissues is a fundamental biological process underlying regeneration. Midkine-a is a cytokine growth factor, whose expression is strongly induced by injury in a variety of tissues across a range of vertebrate classes. Using a zebrafish Midkine-a loss of function mutant, we evaluated regeneration of caudal fin, extraocular muscle and retinal neurons to investigate the function of Midkine-a during epimorphic regeneration. In wildtype zebrafish, injury among these tissues induces robust proliferation and rapid regeneration. In Midkine-a mutants, the initial proliferation in each of these tissues is significantly diminished or absent. Regeneration of the caudal fin and extraocular muscle is delayed; regeneration of the retina is nearly completely absent. These data demonstrate that Midkine-a is universally required in the signaling pathways that convert tissue injury into the initial burst of cell proliferation. Further, these data highlight differences in the molecular mechanisms that regulate epimorphic regeneration in zebrafish.