Signaling centers of limb development and regeneration

Limb loss or deformities are prevalent in our society, impacting 1/190 people. Moreover, due to the rise in diabetes and vascular diseases, amputee numbers are expected to increase. Nonetheless, there is no treatment available other than prosthetics. Although the experimental investigation of limb development and regeneration can offer potential therapies, research on these topics to date has depended heavily on using animals and static data collection, causing many animals to be sacrificed without informing intricate dynamic interactions between cell types. Furthermore, limb regeneration studies involve amputations and need significant refinements for animal welfare. To replace, reduce, and refine animal usage for limb development and regeneration studies, I propose developing explant or in vitro stem-cell-based simplified culture systems. These models will revolutionize limb development and regeneration studies that are historically dependent on animals. Moreover, they will pave the way for studying complex cell-cell interactions shaping limb morphogenesis, and create foundations for future human limb development studies. Finally, to facilitate the adoption and implementation of simplified models by the research community, the projects will use a broad range of approaches including developing user-friendly websites enabling feasible protocol and data sharing. Overall, the proposed projects advance 3Rs, and fulfill the innovation and implementation objectives of NRP79

Tissues and Cell Types of Appendage Regeneration: A Detailed Look at the Wound Epidermis and Its Specialized Forms

Therapeutic implementation of human limb regeneration is a daring aim. Studying species that can regrow their lost appendages provides clues on how such a feat can be achieved in mammals. One of the unique features of regeneration-competent species lies in their ability to seal the amputation plane with a scar-free wound epithelium. Subsequently, this wound epithelium advances and becomes a specialized wound epidermis (WE) which is hypothesized to be the essential component of regenerative success. Recently, the WE and specialized WE terminologies have been used interchangeably. However, these tissues were historically separated, and contemporary limb regeneration studies have provided critical new information which allows us to distinguish them. Here, I will summarize tissue-level observations and recently identified cell types of WE and their specialized forms in different regeneration models

Mechanisms of regeneration: to what extent do they recapitulate development?

One of the enduring debates in regeneration biology is the degree to which regeneration mirrors development. Recent technical advances, such as single-cell transcriptomics and the broad applicability of CRISPR systems, coupled with new model organisms in research, have led to the exploration of this longstanding concept from a broader perspective. In this Review, I outline the historical parallels between development and regeneration before focusing on recent research that highlights how dissecting the divergence between these processes can uncover previously unreported biological mechanisms. Finally, I discuss how these advances position regeneration as a more dynamic and variable process with expanded possibilities for morphogenesis compared with development. Collectively, these insights into mechanisms that orchestrate morphogenesis may reshape our understanding of the evolution of regeneration, reveal hidden biology activated by injury, and offer non-developmental strategies for restoring lost or damaged organs and tissues

Signaling centers of limb development and regeneration

Limb loss or deformities are prevalent in our society, impacting 1/190 people. Moreover, due to the rise in diabetes and vascular diseases, amputee numbers are expected to increase. Nonetheless, there is no treatment available other than prosthetics. Although the experimental investigation of limb development and regeneration can offer potential therapies, research on these topics to date has depended heavily on using animals and static data collection, causing many animals to be sacrificed without informing intricate dynamic interactions between cell types. Furthermore, limb regeneration studies involve amputations and need significant refinements for animal welfare. To replace, reduce, and refine animal usage for limb development and regeneration studies, I propose developing explant or in vitro stem-cell-based simplified culture systems. These models will revolutionize limb development and regeneration studies that are historically dependent on animals. Moreover, they will pave the way for studying complex cell-cell interactions shaping limb morphogenesis, and create foundations for future human limb development studies. Finally, to facilitate the adoption and implementation of simplified models by the research community, the projects will use a broad range of approaches including developing user-friendly websites enabling feasible protocol and data sharing. Overall, the proposed projects advance 3Rs, and fulfill the innovation and implementation objectives of NRP79

Appendage regeneration is context dependent at the cellular level

Species that can regrow their lost appendages have been studied with the ultimate aim of developing methods to enable human limb regeneration. These examinations highlight that appendage regeneration progresses through shared tissue stages and gene activities, leading to the assumption that appendage regeneration paradigms (e.g. tails and limbs) are the same or similar. However, recent research suggests these paradigms operate differently at the cellular level, despite sharing tissue descriptions and gene expressions. Here, collecting the findings from disparate studies, I argue appendage regeneration is context dependent at the cellular level; nonetheless, it requires (i) signalling centres, (ii) stem/progenitor cell types and (iii) a regeneration-permissive environment, and these three common cellular principles could be more suitable for cross-species/paradigm/age comparisons

Signaling centers of limb development and regeneration

Limb loss or deformities are prevalent in our society, impacting 1/190 people. Moreover, due to the rise in diabetes and vascular diseases, amputee numbers are expected to increase. Nonetheless, there is no treatment available other than prosthetics. Although the experimental investigation of limb development and regeneration can offer potential therapies, research on these topics to date has depended heavily on using animals and static data collection, causing many animals to be sacrificed without informing intricate dynamic interactions between cell types. Furthermore, limb regeneration studies involve amputations and need significant refinements for animal welfare. To replace, reduce, and refine animal usage for limb development and regeneration studies, I propose developing explant or in vitro stem-cell-based simplified culture systems. These models will revolutionize limb development and regeneration studies that are historically dependent on animals. Moreover, they will pave the way for studying complex cell-cell interactions shaping limb morphogenesis, and create foundations for future human limb development studies. Finally, to facilitate the adoption and implementation of simplified models by the research community, the projects will use a broad range of approaches including developing user-friendly websites enabling feasible protocol and data sharing. Overall, the proposed projects advance 3Rs, and fulfill the innovation and implementation objectives of NRP79

Signaling centers of limb development and regeneration

Limb loss or deformities are prevalent in our society, impacting 1/190 people. Moreover, due to the rise in diabetes and vascular diseases, amputee numbers are expected to increase. Nonetheless, there is no treatment available other than prosthetics. Although the experimental investigation of limb development and regeneration can offer potential therapies, research on these topics to date has depended heavily on using animals and static data collection, causing many animals to be sacrificed without informing intricate dynamic interactions between cell types. Furthermore, limb regeneration studies involve amputations and need significant refinements for animal welfare. To replace, reduce, and refine animal usage for limb development and regeneration studies, I propose developing explant or in vitro stem-cell-based simplified culture systems. These models will revolutionize limb development and regeneration studies that are historically dependent on animals. Moreover, they will pave the way for studying complex cell-cell interactions shaping limb morphogenesis, and create foundations for future human limb development studies. Finally, to facilitate the adoption and implementation of simplified models by the research community, the projects will use a broad range of approaches including developing user-friendly websites enabling feasible protocol and data sharing. Overall, the proposed projects advance 3Rs, and fulfill the innovation and implementation objectives of NRP79