Autophagy meets planarians

González‐Estévez, Cristina

doi:10.4161/auto.5.3.7665

Cited by 22 publications

(25 citation statements)

References 83 publications

(104 reference statements)

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“…At the molecular level, we recently demonstrated the existence of autophagy and cell death in the planarian species Girardia tigrina through the study of a novel gene, Gtdap-1 [82][83][84][85], the homologue of DAP-1 (death-associated protein-1) in humans. The DAP-1 protein was originally identified, along with the protein DAP-kinase (DAP-2 or DAPk), as a positive mediator of programmed cell death induced by gamma-interferon in HeLa cells [86].…”

Section: Autophagy: Cell Death and Cell Protection In Planariansmentioning

confidence: 99%

Autophagy and apoptosis in planarians

González‐Estévez

Saló

2010

Apoptosis

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Adult planarians are capable of undergoing regeneration and body remodelling in order to adapt to physical damage or extreme environmental conditions. Moreover, most planarians can tolerate long periods of starvation and during this time, they shrink from an adult size to, and sometimes beyond, the initial size at hatching. Indeed, these properties have made them a classic model to study stem cells and regeneration. Under such stressful conditions, food reserves from the gastrodermis and parenchyma are first used up and later the testes, copulatory organs and ovaries are digested. More surprisingly, when food is again made available to shrunken individuals, they grow back to adult size and all their reproductive structures reappear. These cycles of growth and shrinkage may occur over long periods without any apparent impairment to the individual, or to its future maturation and breeding capacities. This plasticity resides in a mesoderm tissue known as the parenchyma, which is formed by several differentiated non-proliferating cell types and only one mitotically active cell type, the neoblasts, which represent approximately 20-30% of the cells in the parenchyma. Neoblasts are generally thought to be somatic stem-cells that participate in the normal continuous turnover of all cell types in planarians. Hence, planarians are organisms that continuously adapt their bodies (morphallaxis) to different environmental stresses (i.e.: injury or starvation). This adaptation involves a variety of processes including proliferation, differentiation, apoptosis and autophagy, all of which are perfectly orchestrated and tightly regulated to remodel or restore the body pattern. While neoblast biology and body re-patterning are currently the subject of intense research, apoptosis and autophagy remain much less studied. In this review we will summarize our current understanding and hypotheses regarding where and when apoptosis and autophagy occur and fulfil an essential role in planarians.

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Section: Autophagy: Cell Death and Cell Protection In Planariansmentioning

confidence: 99%

Autophagy and apoptosis in planarians

González‐Estévez

Saló

2010

Apoptosis

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“…In addition to the formation of new structures at the blastema, homeostatic changes in the old tissue are also necessary for the planarian to remodel its body. Similarly, uninjured planarians constantly replace aged differentiated cells from the mitotic progeny of neoblasts [10]. The extent and duration of mitotic responses, neoblast migration, the differentiation of neoblast progeny and mechanisms to report successful regenerative outcomes that ultimately down regulate growth responses must exist through the whole animal.…”

Section: Introductionmentioning

confidence: 99%

SMG-1 and mTORC1 Act Antagonistically to Regulate Response to Injury and Growth in Planarians

Gonzalez-Estevez

Felix²,

Smith³

et al. 2012

PLoS Genet

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Planarian flatworms are able to both regenerate their whole bodies and continuously adapt their size to nutrient status. Tight control of stem cell proliferation and differentiation during these processes is the key feature of planarian biology. Here we show that the planarian homolog of the phosphoinositide 3-kinase-related kinase (PIKK) family member SMG-1 and mTOR complex 1 components are required for this tight control. Loss of smg-1 results in a hyper-responsiveness to injury and growth and the formation of regenerative blastemas that remain undifferentiated and that lead to lethal ectopic outgrowths. Invasive stem cell hyper-proliferation, hyperplasia, hypertrophy, and differentiation defects are hallmarks of this uncontrolled growth. These data imply a previously unappreciated and novel physiological function for this PIKK family member. In contrast we found that planarian members of the mTOR complex 1, tor and raptor, are required for the initial response to injury and blastema formation. Double smg-1 RNAi experiments with tor or raptor show that abnormal growth requires mTOR signalling. We also found that the macrolide rapamycin, a natural compound inhibitor of mTORC1, is able to increase the survival rate of smg-1 RNAi animals by decreasing cell proliferation. Our findings support a model where Smg-1 acts as a novel regulator of both the response to injury and growth control mechanisms. Our data suggest the possibility that this may be by suppressing mTOR signalling. Characterisation of both the planarian mTORC1 signalling components and another PIKK family member as key regulators of regeneration and growth will influence future work on regeneration, growth control, and the development of anti-cancer therapies that target mTOR signalling.

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“…However, we are still far from an understanding of the mechanics and regulation of this homeostatic plasticity. Several key traits that planarians posses demonstrate the incredible extent of this plasticity (reviewed in (Aboobaker, 2011;Gonzalez-Estevez, 2009;Reddien and Sanchez Alvarado, 2004;Salo, 2006). Most planarians are able to reproduce asexually by fission.…”

Section: Introductionmentioning

confidence: 99%

“…Most planarians are able to reproduce asexually by fission. For instance in Schmidtea mediterranea fission occurs at the post-pharyngeal level, whereby the tail of the animal attaches to the substrate while the head pulls away, resulting in two fragments that will regenerate two complete to their full size when fed (reviewed in (Gonzalez-Estevez, 2009). …”

Section: Introductionmentioning

confidence: 99%

Decreased neoblast progeny and increased cell death during starvation-induced planarian degrowth

González‐Estévez

Felix²,

Rodríguez-Esteban³

et al. 2012

Int. J. Dev. Biol.

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The development of a complex multicellular organism requires a careful coordination of growth, cell division, cell differentiation and cell death. All these processes must be under intricate and coordinated control, as they have to be integrated across all tissues. Freshwater planarians are especially plastic, in that they constantly replace somatic tissues from a pool of adult somatic stem cells and continuously undergo growth and degrowth as adult animals in response to nutrient availability. During these processes they appear to maintain perfect scale of tissues and organs. These life history traits make them an ideal model system to study growth and degrowth. We have studied the unique planarian process of degrowth. When food is not available, planarians are able to degrow to a minimum size, without any signs of adverse physiological outcomes. For example they maintain full regenerative capacity. Our current knowledge of how this is regulated at the molecular and cellular level is very limited. Planarian degrowth has been reported to result from a decrease in cell number rather than a decrease in cell size. Thus one obvious explanation for degrowth would be a decrease in stem cell proliferation. However evidence in the literature suggests this is not the case. We show that planarians maintain normal basal mitotic rates during degrowth but that the number of stem cell progeny decreases during starvation and degrowth. These observations are reversed upon feeding, indicating that they are dependent on nutritional status. An increase in cell death is also observed during degrowth, which is not rapidly reversed upon feeding. We conclude that degrowth is a result of cell death decreasing cell numbers and that the dynamics of neoblast self-renewal and differentiation adapt to nutrient conditions to allow maintenance of the neoblast population during the period of starvation.

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Autophagy meets planarians

Cited by 22 publications

References 83 publications

Autophagy and apoptosis in planarians

Autophagy and apoptosis in planarians

SMG-1 and mTORC1 Act Antagonistically to Regulate Response to Injury and Growth in Planarians

Decreased neoblast progeny and increased cell death during starvation-induced planarian degrowth

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