Regenerative loss in the animal kingdom as viewed from the mouse digit tip and heart

The myriad regenerative abilities across the animal kingdom have fascinated us for centuries. Recent advances in developmental, molecular, and cellular biology have allowed us to unearth a surprising diversity of mechanisms through which these processes occur. Developing an all-encompassing theory of animal regeneration has thus proved a complex endeavor. In this chapter, we frame the evolution and loss of animal regeneration within the broad developmental constraints that may physiologically inhibit regenerative ability across animal phylogeny. We then examine the mouse as a model of regeneration loss, specifically the experimental systems of the digit tip and heart. We discuss the digit tip and heart as a positionally-limited system of regeneration and a temporally-limited system of regeneration, respectively. We delve into the physiological processes involved in both forms of regeneration, and how each phase of the healing and regenerative process may be affected by various molecular signals, systemic changes, or microenvironmental cues. Lastly, we also discuss the various approaches and interventions used to induce or improve the regenerative response in both contexts, and the implications they have for our understanding regenerative ability more broadly.