Regeneration of Organs and Appendages in Zebrafish: A Window into Underlying Control Mechanisms

Abstract

The ability to regenerate organs and appendages is not universal among animals. Humans have a rather limited capacity to regenerate after an injury, while other vertebrates such as the zebrafish are capable of regenerating many anatomical structures. It is unknown why different vertebrates have such differences in regenerative capacity, so studying animal models that do regenerate will allow us to know what is needed to regenerate. Zebrafish research is not only able to tell us what mechanisms are involved in regeneration, but it also shows us that there are different regeneration strategies: some use stem cells while other create progenitors from differentiated tissue cells. This article details how zebrafish uses and regulates either differentiated tissue cells or stem cells to regenerate. We focus on four structures – fin appendage, brain, spinal cord and heart – and describe how current cell and molecular discoveries from these regenerating fish structures contribute to our understanding of general principles of regenerative biology. Key Concepts The zebrafish is a remarkable in vivo model to understand the stem/progenitor cell biology and molecular mechanisms involved in appendage and organ regeneration. Studying how the zebrafish regenerates its fins, its nervous system and its heart will provide information on how endogenous cell populations (whether fully differentiated or stem cells) are activated and concertedly controlled to regenerate compound structures. Different zebrafish tissues use different strategies to regenerate: some convert differentiated tissue cells to progenitor cells while other draw from stem cell pools. Zebrafish appendages and hearts regenerate primarily from the residual differentiated tissues. Zebrafish nervous tissue regenerates from resident stem cell populations.

A regeneration-triggered metabolic adaptation is necessary for cell identity transitions and cell cycle re-entry to support blastema formation and bone regeneration

“…The zebrafish ( Danio rerio ) is a well-established model to study vertebrate regeneration due to its capacity to efficiently regenerate multiple organs and complex tissues, such as the caudal fin ( Sehring and Weidinger, 2020 ; Antos et al, 2016 ; Marques et al, 2019 ). Caudal fin regeneration is an epimorphic process dependent on the formation of a blastema, a transient structure composed of proliferative lineage-restricted progenitor cells that originate from mature cells of the uninjured tissue ( Kawakami, 2010 ; Poss et al, 2003 ).…”

“…The zebrafish (Danio rerio) is a well-established model to study vertebrate regeneration due to its capacity to efficiently regenerate multiple organs and complex tissues, such as the caudal fin (1)(2)(3).…”

Adult neuronal regeneration in the telencephalon of the killifish Aphaniops hormuzensis

“…Traumatic brain injuries (TBI) are disastrous situations that limit the most vertebrate's abilities. While, regeneration of complex body structure is a common phenomenon among the lower vertebrates, such as amphibians and fish (Antos et al, 2001; Endo et al, 2007; Gemberling et al, 2013; Tsonis, 2000), this potential is lost during the vertebrate's evolution and becomes very limited in adult mammals (Ghosh & Hui, 2016).…”

Yap induces osteoblast differentiation by modulating Bmp signalling during zebrafish caudal fin regeneration

“…While mammals show limited ability to regenerate (Zhao et al, 2016), zebrafish (Danio rerio) can regrow multiple organs and tissues upon injury (Antos et al, 2016). Bone is a major tissue in the zebrafish caudal fin (Pfefferli and Jazẃinśka, 2015) and its regeneration relies on dedifferentiation of mature osteoblasts and on the recruitment of resident progenitor cells (Ando et al, 2017;Sousa et al, 2011), which assemble an osteoprogenitor pool.…”