ReviewComplement-triggered pathways orchestrate regenerative responses throughout phylogenesis
Section snippets
Current trends and challenges in regenerative medicine
Regenerative biology defines a rapidly expanding field of research that comes to terms with the very essence of organismic development; the inborn ability of cells and tissues to reprogram their fate, switch into an embryonic-like, pluripotent state, and repopulate damaged or malfunctioning organs through lineage-specific redifferentiation [1].
Regenerative responses culminate through finely orchestrated cellular processes and fate-deciding molecular circuits that are activated in response to
Tissue regeneration in lower vertebrates
Comparative phylogenetic studies have been instrumental in furthering our understanding of the molecular basis of organ regeneration [9], [48]. Regeneration appears to be a primordial attribute of metazoans that has gradually been lost or constrained during phylogeny, as organisms evolved to more complex and energy-demanding structures [8]. Along this trail of evolution, urodele amphibians hold a unique place in view of their capacity to regenerate entire body parts through precise tissue
Insights from liver regeneration models
The mammalian liver is among only a few organs of the adult body that have retained the inherent ability to regenerate in response to acute toxic injury, viral infection, or surgical resection (hepatectomy) [11]. Liver regeneration culminates in the coordinated activation of growth factor-regulated and cytokine-driven pathways that instruct quiescent hepatocytes and other non-parenchymal liver cells (Kupffer cells, endothelial cells) to re-enter the cell cycle and proliferate [11]. The
Concluding remarks and future perspectives
Complement, a primordial sentinel of innate immunity, has long been perceived as a mere “executioner” that directly neutralizes pathogens or tags them to promote their phagocytosis. However, over the past two decades, complement biology has undergone a drastic reorientation by recapitulating old developmental paradigms from a systems-wide perspective. Emerging evidence from various animal models points to a more subtle role of this innate immune system in basic development, vertebrate
Acknowledgments
We would like to thank Dr. Deborah McClellan for excellent editorial assistance, as well as current and past laboratory members for contributing to the research discussed in this article. This work was supported by NIH grants AI003040, AI068730, AI072106, AI097805, EY020633, GM097747, and DE021685 for JDL.
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