Cell plasticity in homeostasis and regeneration

Abstract

SUMMARYOver the past decades, genetic analyses performed in vertebrate and invertebrate organisms deciphered numerous cellular and molecular mechanisms deployed during sexual development and identified genetic circuitries largely shared among bilaterians. In contrast, the functional analysis of the mechanisms that support regenerative processes in species randomly scattered among the animal kingdom, were limited by the lack of genetic tools. Consequently, unifying principles explaining how stress and injury can lead to the reactivation of a complete developmental program with restoration of original shape and function remained beyond reach of understanding. Recent data on cell plasticity suggest that beside the classical developmental approach, the analysis of homeostasis and asexual reproduction in adult organisms provides novel entry points to dissect the regenerative potential of a given species, a given organ or a given tissue. As a clue, both tissue homeostasis and regeneration dynamics rely on the availability of stem cells and/or on the plasticity of differentiated cells to replenish the missing structure. The freshwater Hydra polyp provides us with a unique model system to study the intricate relationships between the mechanisms that regulate the maintenance of homeostasis, even in extreme conditions (starvation and overfeeding) and the reactivation of developmental programs after bisection or during budding. Interestingly head regeneration in Hydra can follow several routes according to the level of amputation, suggesting that indeed the homeostatic background dramatically influences the route taken to bridge injury and regeneration.Mol.

The Hydra model: disclosing an apoptosis-driven generator of Wnt-based regeneration

“…Also in Hydra the recent possibility to establish transgenic strains allows investigators to follow live the cellular remodeling that takes place Box 1: Phylogenetic tree showing the animal phyla that contain species with high regenerative potential. All species schematized here provide useful model systems to study the biology of adult stem cells and the mechanisms supporting adult regeneration 1,2,31,57,70 . By contrast Caudata (Xenopus) and Insects (Drosophila, cricket) only regenerate their appendages at the larval stage but provide valuable model systems to test the impact of extinguishing developmental processes on regenerative programs 73 and to dissect the genetic pathways involved in apoptosis-induced compensatory proliferation [58][59][60] .…”

“…More generally, this strongly suggests that the regenerative route taken after injury is actually dramatically influenced by the homeostatic context 70 . On the basis of the above argument, we propose here a tri-modular organization of regenerative processes that would be applicable to most if not all contexts (Box Fig.1): we see regeneration as a highly dynamic bridging process between two boundary markers -the wound healing process and the re-development of the missing structure -which definitively need to be connected 71 .…”

Entre homéostasie et développement, quelles stratégies pour régénérer ?

“…Ceci a été démontré initialement chez l'oursin (Driesch, 1900), puis ensuite chez le Xénope, le poulet et les embryons de mammifères (voir Galliot & Ghila, 2010).…”

“…Tandis que la réparation tissulaire et la régénération sont induites par des forces externes (blessure, lésions tissulaires, amputation), le renouvellement tissulaire qui résulte de la combinaison de la prolifération, de la mort et de la différenciation cellulaires, répond plus généralement à des signaux endogènes (Pellettieri & Sanchez Alvarado, 2007). (Tanaka and Ferretti, 2009;Galliot and Ghila, 2010).…”

“…De façon plus générale, le fait que le contexte homéostatique contraigne les voies possibles de régénération met en évidence une interaction entre mécanismes homéostatiques et programmes de développement qui apparaît comme une signature propre au phénomène de régénération, quel que soit le système utilisé comme modèle (Galliot & Ghila, 2010;Bergmann & Steller, 2010). Cette façon de considérer les processus régénératifs explique pourquoi la régénération ne peut être réduite à un processus de patterning ou à une dynamique des cellules souches.…”