Gtdap-1 and the Role of Autophagy During Planarian Regeneration and Starvation

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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.

Section: Introductionsupporting

confidence: 54%

Section: Planarian Degrowth Correlates With An Increase In Cell Deathmentioning

confidence: 99%

Section: Planarian Degrowth Correlates With An Increase In Cell Deathmentioning

confidence: 99%

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

González‐Estévez

Felix²,

Rodríguez-Esteban³

et al. 2012

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“…Although whole-mount in situ hybridization (ISH) is a powerful technique for detecting gene expression in planarians (Umesono et al, 1997;Sánchez Alvarado et al, 2002;González-Estévez et al, 2007), sub-cellular localization of transcripts has not been previously described in these organisms. For instance, in Drosophila, typical mRNAs are predominantly observed in the cytoplasm but primary miRNA transcripts have been detected as nascent transcripts at each chromosomal locus in the nucleus (Kosman et al, 2004;Ronshaugen and Levine, 2004).…”

Section: Introductionmentioning

confidence: 99%

Diverse miRNA spatial expression patterns suggest important roles in homeostasis and regeneration in planarians

González‐Estévez¹,

Arseni²,

Thambyrajah³

et al. 2009

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miRNAs are an important class of non-protein coding small RNAs whose specific functions in animals are rapidly being elucidated. It is clear that miRNAs can play crucial roles in stem cell maintenance, cell fate determination and differentiation. We use planarians, which possess a large population of pluripotent somatic stem cells, as a powerful model system to study many aspects of stem cell biology and regeneration. In particular we wish to investigate the regulatory role miRNAs may have in planarian stem cell self renewal, proliferation and differentiation. Here, we characterized the differential spatial patterns of expression of miRNAs in whole and regenerating planarians by in situ hybridization to nascent miRNA transcripts. These miRNA expression patterns are the first which have been determined for a Lophotrocozoan animal. We have characterized the expression patterns of 42 miRNAs in adult planarians, constituting a complete range of tissue specific expression patterns. We also followed miRNA expression during planarian regeneration. The majority of planarian miRNAs were expressed either in areas where stem cells (neoblasts) are located and/or in the nervous system. Some miRNAs were definitively expressed in stem cells and dividing cells as confirmed by in situ hybridisation after irradiation. We also found miRNAs to be expressed in germ stem cells of the sexual strain. Together, these data suggest an important role for miRNAs in stem cell regulation and in neural cell differentiation in planarians.

“…GtDap-1 Cells in autophagy, induces cell death (González-Estévez et al, 2007a, González-Estévez et al, 2007b, Tettamanti et al, 2008 miRNAs let-7 Gt Let-7 Not determined (Pasquinelli et al, 2003) TABLE 1…”

Section: Gtmentioning

confidence: 99%

Planarian regeneration: achievements and future directions after 20 years of research

Saló¹,

Abril²,

Adell³

et al. 2009

104

Planarians can undergo dramatic changes in body size and regenerate their entire body plan from small pieces after cutting. This remarkable morphological plasticity has made them an excellent model in which to analyze phenomena such as morphogenesis, restoration of pattern and polarity, control of tissue proportions and tissue homeostasis. They have a unique population of pluripotent stem cells in the adult that can give rise to all differentiated cell types, including the germ cells. These cellular characteristics provide an excellent opportunity to study the mechanisms involved in the maintenance and differentiation of cell populations in intact and regenerating animals. Until recently, the planarian model system lacked opportunities for genetic analysis; however, this handicap was overcome in the last decade through the development of new molecular methods which have been successfully applied to planarians. These techniques have allowed analysis of the temporal and spatial expression of genes, as well as interference with gene function, generating the first phenotypes by loss or gain of function. Finally, the sequencing of the planarian genome has provided the essential tools for an in-depth analysis of the genomic regulation of this model system. In this review, we provide an overview of planarians as a model system for research into development and regeneration and describe new lines of investigation in this area.