Autophagy Required for Zebrafish Regeneration

Zebrafish are studied for their exceptional regenerative capacity, as researchers are attempting to determine whether we mammals have similar, dormant abilities to regenerate limbs and organs, or whether there is any other way to port this ability into human tissues. The first step on this path is to catalog the molecular biology of zebrafish regeneration: how exactly it works under the hood. This research is a part of these efforts:

Regeneration is the ability of multicellular organisms to replace damaged tissues and regrow lost body parts. This process relies on cell fate transformation that involves changes in gene expression as well as in the composition of the cytoplasmic compartment, and exhibits a characteristic age-related decline. Here, we present evidence that genetic and pharmacological inhibition of autophagy - a lysosome-mediated self-degradation process of eukaryotic cells, which has been implicated in extensive cellular remodelling and aging - impairs the regeneration of amputated caudal fins in the zebrafish. Thus, autophagy is required for injury-induced tissue renewal.

We further show that upregulation of autophagy in the regeneration zone occurs downstream of mitogen-activated protein kinase/extracellular signal-regulated kinase signalling to protect cells from undergoing apoptosis and enable cytosolic restructuring underlying terminal cell fate determination. This novel cellular function of the autophagic process in regeneration implies that the role of cellular self-digestion in differentiation and tissue patterning is more fundamental than previously thought.



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