Xenopus laevis il11ra.L is an experimentally proven interleukin-11 receptor component that is required for tadpole tail regeneration

Shunya Suzuki,Takeo Kubo,Kayo Sasaki,Taro Fukazawa

doi:10.1038/s41598-022-05954-w

Abstract

Xenopus laevis tadpoles possess high regenerative ability and can regenerate functional tails after amputation. An early event in regeneration is the induction of undifferentiated cells that form the regenerated tail. We previously reported that interleukin-11 (il11) is upregulated immediately after tail amputation to induce undifferentiated cells of different cell lineages, indicating a key role of il11 in initiating tail regeneration. As Il11 is a secretory factor, Il11 receptor-expressing cells are thought to mediate its function. X. laevis has a gene annotated as interleukin 11 receptor subunit alpha on chromosome 1L (il11ra.L), a putative subunit of the Il11 receptor complex, but its function has not been investigated. Here, we show that nuclear localization of phosphorylated Stat3 induced by Il11 is abolished in il11ra.L knocked-out culture cells, strongly suggesting that il11ra.L encodes an Il11 receptor component. Moreover, knockdown of il11ra.L impaired tadpole tail regeneration, suggesting its indispensable role in tail regeneration. We also provide a model showing that Il11 functions via il11ra.L-expressing cells in a non-cell autonomous manner. These results highlight the importance of il11ra.L-expressing cells in tail regeneration.

Highlights

Organ regenerative ability varies among animal species
The corresponding genes in X. laevis are il11ra.L, il6st.L, il6st.S, jak[1].L, jak[1].S, jak[2].L, jak[2].S, stat[3].S, and stat[3].L, and reverse transcription-polymerase chain reaction (PCR) confirmed that these genes are expressed in XTC-YF (Fig. 1A, S1A)
We assessed tissue regeneration by measuring the side view area of the whole regenerated tail, the muscles and the notochord in the regenerated tails, and found that the regenerated tails in the KD group were significantly smaller, and had smaller muscles and notochord (Fig. 2H–J), indicating that the il11ra.L KD affected muscle and notochord regeneration. These results strongly suggested that il11ra.L is necessary for tadpole tail regeneration, and suggesting that X. laevis Il11 receptor subunit alpha (Il11ra).L functions as an Il11 receptor component in tadpole tail regeneration

Summary

Introduction

Organ regenerative ability varies among animal species. Among vertebrates, fish and amphibians possess high regenerative ability, whereas mammals have restricted regenerative a bility[1,2,3]. A recent single-cell resolution analysis of tail regeneration revealed no evidence for the emergence of multipotent progenitors or intermediate cell states suggesting transdifferentiation[8] These findings suggest that lineage-restricted tissue stem cells or precursors are major contributors to tail regeneration in X. laevis tadpoles[6,7,8,9]. After tail amputation, these precursors are activated to generate a mass of undifferentiated proliferating cells at the wound stump to form the regeneration bud, and differentiate to the tissues from which they are d erived[6,7]. We offer a possible model of il11ra.L-expressing cell function in tadpole tail regeneration

Methods

Results

Conclusion