Chapter 22: Regeneration: Mechanisms of Tissue Renewal

Regeneration: Mechanisms of Tissue Renewal categorizes regeneration into four primary modes: stem-cell mediated, epimorphosis, morphallaxis, and compensatory growth. In simple organisms like Hydra, regeneration occurs through morphallaxis and is guided by morphogenetic gradients where the hypostome acts as a head organizer, primarily driven by Wnt signaling through the beta-catenin pathway. Planarian flatworms showcase a different strategy, relying on adult pluripotent stem cells called clonogenic neoblasts. These worms use a complex signaling axis involving Wnt and its inhibitor Notum, along with Erk signaling, to establish head-to-tail polarity during reconstruction. Turning to complex vertebrates, the salamander limb undergoes epimorphosis by forming a regeneration blastema through cell dedifferentiation. Notably, these blastema cells retain memory of their original tissue type, and their successful proliferation depends on the presence of the apical epidermal cap and nerve-derived mitogens like newt anterior gradient protein, or nAG. Zebrafish provide further insights into organ-specific repair, demonstrating that heart regeneration involves the proliferation of preexisting cardiomyocytes and, in larval stages, the transdifferentiation of atrial cells into ventricular cells via Notch-Delta signaling. Finally, the chapter contrasts these abilities with mammalian systems, which largely rely on compensatory regeneration, most famously observed in the liver. Mammalian liver growth is driven by the division of mature hepatocytes rather than blastema formation and is regulated by systemic factors such as bile acids acting through Fxr transcription factors. Collectively, the study of these diverse model systems highlights the potential for future medical applications in human tissue repair by harnessing embryonic-like signaling pathways.