Heterogeneous fates and dynamic rearrangement of regenerative epidermis-derived cells during zebrafish fin regeneration

Abstract

The regenerative epidermis (RE) is a specialized tissue that plays an essential role in tissue regeneration. However, the fate of the RE during and after regeneration is unknown. In this study, we performed Cre--mediated cell fate tracking and revealed the fates of a major population of the RE cells that express () during zebrafish fin regeneration. Our study showed that these RE cells are mainly recruited from the inter-ray epidermis, and that they follow heterogeneous cell fates. Early recruited cells contribute to initial wound healing and soon disappear by apoptosis, while the later recruited cells contribute to the regenerated epidermis. Intriguingly, many of these cells are also expelled from the regenerated tissue by a dynamic caudal movement of the epidermis over time, and in turn the loss of epidermal cells is replenished by a global self-replication of basal and suprabasal cells in fin. De-differentiation of non-basal epidermal cells into the basal epidermal cells did not occur during regeneration. Overall, our study reveals the heterogeneous fates of RE cells and a dynamic rearrangement of the epidermis during and after regeneration.

Basal epidermis collective migration and local Sonic hedgehog signaling promote skeletal branching morphogenesis in zebrafish fins

“…Zebrafish fin ray branching provides an accessible context to define mechanisms of appendage patterning and skeletal morphogenesis. Our current and earlier study (Armstrong et al, 2017) The directly observed distal movement and likely shedding of fins' basal epidermis, as previously surmised during regeneration (Armstrong et al, 2017;Shibata et al, 2018) is intriguing both functionally and mechanistically. Functionally, continuous bEp replacement may enable rapid recovery from frequent environmental insults.…”

Cellular diversity of the regenerating caudal fin

“…3A and fig. S1B) (15,16). By integrating cells from all stages during regeneration, we found clusters of cells that corresponded to all three layers of the epithelium after injury (Fig.…”

“…Epithelial cells are from three transcriptionally distinct subgroups, representing the superficial (krt4), intermediate (tp63), and basal layers (tp63 and krtt1c19e) of the epithelium (fig. S1, A and B) (15,16).…”

Recent advancements in understanding fin regeneration in zebrafish

“…In addition to the recruitment of neutrophils and macrophages, one of the earliest responses to the injury is the migration of epithelial cells, which form an epithelium covering the wound (Figure 2a) (Poleo, Brown, Laforest, & Akimenko, 2001;Shibata, Ando, Murase, & Kawakami, 2018). Within the next hours to days, the epithelium becomes a multilayered structure, termed the wound or regeneration epidermis (Chen et al, 2015;Shibata, Ando, et al, 2018). In contrast to mammalian limb injury, which is associated with local tissue degradation (Simkin et al, 2015), in zebrafish the regeneration process starts immediately after wound closure.…”