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Cell Plasticity in Homeostasis and Regeneration

By Lewis Kelley,2014-06-02 17:39
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Cell Plasticity in Homeostasis and Regeneration

    REVIEW ARTICLE

    Molecular Reproduction & Development 77:837855 (2010)

Cell Plasticity in Homeostasis and Regeneration

BRIGITTE GALLIOT,* AND LUIZA GHILA

     Faculty of Sciences, Department of Zoology and Animal Biology, University of Geneva, Geneva, Switzerland

SUMMARY

    Over the past decades, genetic analyses performed in vertebrate and invertebrate organisms deciphered numerous cellular and molecular mechanisms deployed The ability of an organism to during sexual development and identied genetic circuitries largely shared among regenerate depends on its bilaterians. In contrast, the functional analysis of the mechanisms that support capacity to access a source of regenerative processes in species randomly scattered among the animal kingdom, stem cells and/or to reprogram were limited by the lack of genetic tools. Consequently, unifying principles explaining differentiated cells 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 * Corresponding author: given species, a given organ or a given tissue. As a clue, both tissue homeostasis and Sciences III, regeneration dynamics rely on the availability of stem cells and/or on the plasticity of 4 Bd dYvoy, CH-1211 differentiated cells to replenish the missing structure. The freshwater Hydra polyp Geneva 4, Switzerland. provides us with a unique model system to study the intricate relationships between E-mail: brigitte.galliot@unige.ch the mechanisms that regulate the maintenance of homeostasis, even in extreme conditions (starvation and overfeeding) and the reactivation of developmental pro- grams 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. Reprod. Dev. 77: 837855, 2010. ß 2010 Wiley-Liss, Inc. Published online in 2 July 2010 Wiley Online Library (wileyonlinelibrary.com). Received 10 December 2009; Accepted 1 May 2010 DOI 10.1002/mrd.21206

    meaning that the differentiated cells can undergo cell growth INTRODUCTION TO ADULT DEVELOPMENTAL

    but no proliferation during adulthood. The nematodes that BIOLOGY

    keep their number of somatic cells constant in adulthood, A wide range of distinct biological processes contribute to provide the best example; similarly, in Drosophila all somatic the preservation of the anatomical form and functionality in adult tissues are post-mitotic except the gut. This drastic adult animal organisms; these processes are acting at regulation of adult cell number generally impedes adult different levels, such as metabolism that affects the whole plasticity, which is required for homeostatic or regenerative organism, cell turnover of organs and tissues, autophagy of mechanisms. However, in most metazoan species, the main specic cell types, DNA repair at the nuclear level (Rando, way to protect adult organisms from physiological dysfunc- 2006). As human beings, we often consider that a high cell tions involves the removal and replacement of old or dam- turnover is an obligatory rule to maintain the integrity of adult organisms. However, this is certainly not systematically observed across animal phyla as several species with short Abbreviations: AEC, apical epithelial cap; ASC, adult stem cell; GRN, gene lifespan can be strictly post-mitotic after development, regulatory network.

ß 2010 WILEY-LISS, INC.

Molecular Reproduction & Development ALLIOT AND GHILA G

    aged differentiated cells. This ongoing physiological force and to maintain the change after this force has ceased replacement process is named cell turnover. The adult stem to act’’ (from Littre French dictionary, translated by Will et al., cells (ASCs) play a key role in this turnover, although limited 2008). At the rst look, this denition apparently applies quite to the organ or the tissue where they reside (Wagers and well to the regenerative process, however, the usage of the Weissman, 2004; Ohlstein and Spradling, 2006; Blanpain word plasticity in biology is much broader, focusing on the et al., 2007). As a classical scenario, ASCs divide through ability of living organisms to adapt to constraints by changing asymmetric division, with one of the daughter cells keeping their organization at a specic level, for example, evolution- the ‘‘stemness’’ status (self-renewal) whereas the second ary, developmental, phenotypic, synaptic, cellular, and mo- one, no longer a stem cell, undergoes a series of cell division, lecular. As a consequence, the word ‘‘plasticity’’ should

    providing a transient amplifying stock that will subsequently never be used alone but always be specied by the level

    commit to one or a series of differentiated fates (Raff, 2003). where it applies (Pomerantz and Blau, 2004). Some As a consequence three competitive processes regulate scientists even proposed to apply to the concept of plasticity homeostasis: cell death, cell proliferation, and cell differen- in biological systems a more ‘‘engineer-oriented’’ usage,

    tiation. The study of their crosstalk in Drosophila imaginal restricting it to the contexts where lasting structural reorga- discs showed how a coordinated cellcell signaling tightly nization, that is, modications of the material structure of regulates this competition in a given tissue (Moreno and the system (interface, connectivity network, constitutive Basler, 2004). In mammalian tissues, cell turnover occurs in elements), are indeed proven, leaving out of plasticity the epidermis, intestine, lung, blood, bone marrow, thymus, effects of variability, flexibility, systematic variations, and testis, uterus, and mammary gland with large variations in vicarious (substituted) processes as these effects rather the rate of cell turnover, from few days for the intestinal result from ‘‘operational’’ than structural changes (Will

    epithelium up to several months for the lung epithelium et al., 2008). We selected here few examples to discuss (Blanpain et al., 2007). In other organs (brain, heart, pan- this view, certainly more rigorous or at least less metaphoric creas, kidney, cornea, etc.), the physiological cell turnover is (following the words of Will et al., 2008) but as we will see, likely limited and/or very slow, making difcult the in vivo difcult to apply in some contexts.

    monitoring of the respective behaviors of stem cells and Evolutionary plasticity is certainly the best example of dying cells. plasticity with structural changes leading to lasting changes. Similar to cell turnover, tissue repair also allows tissue The combination of genomic, genetic, and developmental replacement but requires the damage-induced activation of approaches over the past 20 years have denitively proven

    programs that monitor cell proliferation and cell differentia- that variations in the genomic organization of the Hox gene tion. Finally, regeneration of anatomical structures like clusters obviously lead to genetic reprogramming during appendages, represent an even more complex process with development and to species-specic modications of the

    formation of a transient proliferative structure, the blastema, body plan (Duboule, 2007). Developmental plasticity that and activation of a developmental program that leads to was identied rst in sea urchin embryos by Driesch in 1892, restoration of original shape and function (Brockes and and later in vertebrate embryos, refers to the embryonic Kumar, 2005). Both tissue repair and regeneration that potential for regulation as the embryonic cells at early stages affect different tissue types and require cell replacement on have the ability to change their fate to compensate for cell a large-scale, are triggered by nonspecic and usually loss (Driesch, 1900). This potential, which accounts for the exogenous damage, whereas cell turnover is a process that occurrence of homozygous twins, is transient but can still be is endogenously initiated and restricted to a fraction of cells observed at later stages in more specialized tissues as limb (Pellettieri and Sanchez Alvarado, 2007). buds (Summerbell, 1981) or neural crest cells (Vaglia and Nevertheless one can intuitively perceive a progression Hall, 1999). Developmental plasticity, more recently named from basic tissue self-renewal to tissue repair, reached by transfating (Keleher and Stent, 1990), requires the activation some but not all organs, to regeneration, accessed by a of the gene regulatory network (GRN) that corresponds to

    the new cell fate. Interestingly, in sea urchin embryo this ‘‘happy few’’ elite of organs or structures. This view suggests

    a possible continuum between the processes that regulate activation apparently depends on inputs that are distinct each step, even though their complexity is supposed to during normal and regulative developments (Ettensohn gradually increase. To challenge the solidity of this view, et al., 2007). If conrmed as a general rule, this would mean we review some results recently obtained in the paradig- that context-specic signals sensed at the ‘‘interface’’ of the

    matic Hydra model system. But before considering the system induce long-lasting structural reorganizations of the different forms of plasticity deployed in Hydra, we will rst developing organism.

    discuss the origin and the current meaning of the concept of Phenotypic plasticity is ‘‘the property of a given genotype plasticity. Indeed, this concept is widely used by biologists to produce different phenotypes in response to distinct from different elds, but sometimes covering quite distinct environmental conditions’’ (Metcalf, 1906), with the rst

    meanings. study of adaptive phenotypic plasticity described in the

     crustacean Daphnia. However, the different phenotypes

     might reveal an intrinsic ‘‘repertoire of competences’’ that The Ambiguities of the Concept of ‘‘Plasticity’’ need no structural changes to be expressed (Will et al., The word ‘‘plasticity’’ (from Latin plasticus or Greek 2008). In the same year, 1906, the term neuroplasticity was plastikos, ability to mold) refers to the ‘‘capacity of distortable proposed by Ernesto Lugaro, a psychiatrist, who referred to bodies to change their shape under the action of an external the changes in neural activity during psychic maturation,

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    cell states before and after transdifferentiation (Wagers and learning processes, or post-damage recovery (Berlucchi,

    2002). During the rst half of the 1900s, the concept of brain Weissman, 2004; Slack, 2007). In fact, the most compelling plasticity was rejected by the scientic community, as it was evidence is provided by the transient co-expression of unanimously accepted that the fully developed brain markers of the two differentiated cell states (Schmid and reached stability at adulthood, each region of the brain Alder, 1984).

    performing specic function(s) that could not be modied. More recently, it was possible to induce transdifferentia- In the 1960s, this view started to be challenged by experi- tion by overexpressing one or several cell-specic transcrip-

    ments proving activity-dependent brain plasticity (Bennett tion factors that sufce to convert one cell type to another et al., 1964; Bach-y-Rita et al., 1969). Synaptic plasticity, the (Slack, 2007; Eberhard and Tosh, 2008; Zhou et al., 2008). capability for a neuron to modify on the long term its Indeed nuclear reprogramming plays an essential role in electrophysiological activity according to the stimuli it had cellular plasticity and developmental biologists actually received, was rst studied in the mollusk Aplysia (Bruner and provided the rst experimental evidence of this event: they Tauc, 1965; Kandel and Tauc, 1965). The choice of this showed that nuclei isolated from mature somatic cells