Learning from regenerators · Zebrafish

Small fish. Big regenerative power.

Zebrafish can rebuild damaged or lost parts of their body throughout adult life, including fins, heart muscle and retina. That makes them one of the most widely used animals for studying how regeneration works.

EstablishedDanio rerio

Illustration of a zebrafish with magnified callouts for the heart, retina and fins. — Zebrafish (*Danio rerio*) with the heart, retina and fins highlighted. Illustration, not to scale.

Scientific name: Danio rerio
Group: Freshwater bony fish (teleost)
Regenerates: Fins, heart muscle, retina
Why it is studied: Strong regeneration in adulthood, with well-developed genetic tools

Up close

Region by region, magnified.

What each highlighted part of the zebrafish can do, how it does it and what the research shows.

Magnified illustration of a zebrafish heart

01 Heart

Heart muscle that grows back.

When part of the zebrafish heart is removed, the missing muscle is rebuilt rather than replaced by a permanent scar.

What regenerates: Ventricular heart muscle. In the landmark study, hearts fully regenerated within two months after about 20% of the ventricle was removed.
How: Existing heart-muscle cells (cardiomyocytes) multiply at the edge of the wound and form new muscle.
Compared with mammals: After cardiac injury, mammals typically form scar tissue, with minimal regeneration of heart muscle.

Source: Poss et al., 2002

Magnified illustration of a zebrafish eye

02 Retina

A retina that repairs itself.

The retina is the light-sensing tissue at the back of the eye. In zebrafish, damaged retina can be rebuilt and vision restored.

What regenerates: All major types of retinal neuron, including the photoreceptors that detect light.
How: Support cells called Müller glia are reprogrammed after injury. They take on stem-cell characteristics and produce progenitor cells that become new neurons.
Compared with mammals: Mammalian Müller glia can respond to injury, but their capacity to produce new neurons is meagre and not enough to repair a damaged retina.

Müller glia up close

Source: Goldman, 2014

Magnified illustration of a zebrafish tail fin

03 Fins

Fins that regrow in full.

Fin regeneration is the classic zebrafish model: after amputation, the fin grows back with its original structure.

What regenerates: The fin's bony rays, together with the skin, connective tissue, blood vessels and nerves within it.
How: Cells at the wound form a blastema, a zone of progenitor cells that multiplies and is patterned to rebuild the missing structure.
Why it is useful: Fins are accessible, regrow quickly and can be studied repeatedly, which makes them practical for working out the genes and signals behind regeneration.

Source: Poss et al., 2003

Proposed

Why it matters to us.

Zebrafish and mammals share many of the same cell types and genes. The zebrafish shows that a vertebrate heart and retina can be rebuilt; the open question is why the same tissues in adult mammals usually scar instead.

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Sources

Where this comes from.

Poss KD, Wilson LG, Keating MT. Heart regeneration in zebrafish. Science. 2002;298(5601):2188–2190. doi.org/10.1126/science.1077857
Poss KD, Keating MT, Nechiporuk A. Tales of regeneration in zebrafish. Developmental Dynamics. 2003;226(2):202–210. doi.org/10.1002/dvdy.10220
Goldman D. Müller glial cell reprogramming and retina regeneration. Nature Reviews Neuroscience. 2014;15(7):431–442. doi.org/10.1038/nrn3723

Summaries are simplified for a general audience. Illustrations are artistic, not anatomical drawings.

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