Autophagy and apoptosis in planarians

Cristina Gonzalez-Estevez1 and Emili Salo

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 . . .

Link to full article.

Flow cytometry methods for the study of cell-cycle parameters of planarian stem cells.

Hara Kang; Alejandro Sánchez Alvarado

Due to their characteristic inaccessibility and low numbers, little is known about the cell-cycle dynamics of most stem cells in vivo. A powerful, established methodology to study cell-cycle dynamics is flow cytometry, which is used routinely to study the cell-cycle dynamics of proliferating cells in vitro. Its use in heterogeneous mixtures of cells obtained from whole animals, however, is complicated by the relatively low abundance of cycling to non-cycling cells. We report on flow cytometric methods that take advantage of the abundance of proliferating stem cells in the planarian Schmidtea mediterranea. The optimized protocols allow us to measure cell-cycle dynamics and follow BrdU-labeled cells specifically in complex mixtures of cells. These methods expand on the growing toolkit being developed to study stem cell biology in planarians, and open the door to detailed cytometric studies of a collectively totipotent population of adult stem cells in vivo.

Link to full article.

Planarian Hh Signaling Regulates Regeneration Polarity and Links Hh Pathway Evolution to Cilia

Jochen C. Rink, Kyle A. Gurley, Sarah A. Elliott, Alejandro Sánchez Alvarado

The Hedgehog (Hh) signaling pathway plays multiple essential roles during metazoan development, homeostasis, and disease. Although core protein components are highly conserved, the variations in Hh signal transduction mechanisms exhibited by existing model systems (Drosophila, fish, and mammals) are difficult to understand. We characterized the Hh pathway in planarians. Hh signaling is essential for establishing the anterior/posterior axis during regeneration by modulating wnt expression. Moreover, RNA interference methods to reduce signal transduction proteins Cos2/Kif27/Kif7, Fused, or Iguana do not result in detectable Hh signaling defects; however, these proteins are essential for planarian ciliogenesis. Our study expands the understanding of Hh signaling in the animal kingdom and suggests an ancestral mechanistic link between Hh signaling and the function of cilia.

Link to full article.

Retinoic acid as a regulator of planarian morphogenesis

Ermakova, O.N., et al.

The effect of retinoic acid on regeneration of two species of asexual planarian races, Girardia tigrina and Schmidtea mediterranea, was studied. It was established that retinoic acids at physiological concentrations (10−7–10−10 M) inhibit the regeneration of the head part of planarians but have no effect on tail blastema growth. It is shown that regeneration of the head part is inhibited as a result of arrest of the cell cycle of neoblasts, proliferating stem cells, during the transition from the G 1/G 0 to the S phase. Thus, the morphogenetic role of retinoic acids in planarians, primitive bilaterally symmetrical animals, has been demonstrated.

Full article here.

Figuring out the Heads or Tails Decision in Regeneration

. . . To study how planaria regrow their bodies from a sliver of tissue, Christian Petersen, a postdoctoral fellow in Whitehead Member Peter Reddien's lab, looked at two of the planaria's genes, wntP-1 and wntP-2. These genes act to control cell to cell communication in a process called the Wnt signaling pathway, which is involved in many biological events, including development and growth. Petersen and Reddien had theorized that at least some portion of the Wnt pathway plays a role in regeneration.

In earlier work with planaria, Petersen and Reddien showed that a Wnt-related gene, called Smed-beta-catenin-1 (beta catenin), is necessary for planaria to regenerate a tail instead of a head after tail amputation. This ability to grow a head when the head is cut off and grow a tail when the tail is cut off is known as "regeneration polarity". In this experiment, Petersen cut the head, tail or both the head and tail off of planaria and observed where wntP-1 gene expression occurred. . .

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High-resolution profiling and discovery of planarian small RNAs

Friedländer, M.; Hirst, M.; Marra, M.; Nusbaum, C.; et al.

Freshwater planarian flatworms possess uncanny regenerative capacities mediated by abundant and collectively totipotent adult stem cells. Key functions of these cells during regeneration and tissue homeostasis have been shown to depend on PIWI, a molecule required for Piwi-interacting RNA (piRNA) expression in planarians. Nevertheless, the full complement of piRNAs and microRNAs (miRNAs) in this organism has yet to be defined. Here we report on the large-scale cloning and sequencing of small RNAs from the planarian Schmidtea mediterranea, yielding altogether millions of sequenced, unique small RNAs. We show that piRNAs are in part organized in genomic clusters and that they share characteristic features with mammalian and fly piRNAs. We further identify 61 novel miRNA genes and thus double the number of known planarian miRNAs . . .

Deep sequencing identifies new and regulated microRNAs in Schmidtea mediterranea

Yi-Chien Lu , Magda Smielewska, Dasaradhi Palakodeti, Michael T. Lovci, Stefan Aigner, Gene W. Yeo and Brenton R. Graveley

MicroRNAs (miRNAs) play important roles in directing the differentiation of cells down a variety of cell lineage pathways. The planarian Schmidtea mediterranea can regenerate all lost body tissue after amputation due to a population of pluripotent somatic stem cells called neoblasts, and is therefore an excellent model organism to study the roles of miRNAs in stem cell function. Here, we use a combination of deep sequencing and bioinformatics to discover 66 new miRNAs in S. mediterranea. We also identify 21 miRNAs that are specifically expressed . . .

Abstract and full article available here.

Molecular Analysis of Stem Cells and Their Descendants during Cell Turnover and Regeneration in the Planarian Schmidtea mediterranea

Molecular Analysis of Stem Cells and Their Descendants during Cell Turnover and Regeneration in the Planarian Schmidtea mediterranea

George T. Eisenhoffer, Hara Kang, and Alejandro Sanchez Alvarado

In adult planarians, the replacement of cells lost to physiological turnover or injury is sustained by the proliferation and differentiation of stem cells known as neoblasts. Neoblast lineage relationships and the molecular changes that take place during differentiation into the appropriate cell types are poorly understood. Here we report the identification and characterization of a cohort of genes specifically expressed in neoblasts and their descendants. We find that genes with severely downregulated expression after irradiation molecularly define at least three discrete subpopulations of cells. Simultaneous BrdU labeling and . . .

The article in PDF format can be accessed here.

Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling

Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling

Néstor J. Oviedo, Bret J. Pearson, Michael Levin, and Alejandro Sánchez Alvarado

We have identified two genes, Smed-PTEN-1 and Smed-PTEN-2, capable of regulating stem cell function in the planarian Schmidtea mediterranea. Both genes encode proteins homologous to the mammalian tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Inactivation of Smed-PTEN-1 and -2 by RNA interference (RNAi) in planarians disrupts regeneration, and leads to abnormal outgrowths in both cut and uncut animals followed soon after by death (lysis). The resulting phenotype is characterized by hyperproliferation of neoblasts (planarian stem cells), tissue disorganization and a significant accumulation of postmitotic cells with impaired differentiation capacity. Further analyses revealed . . .

The article is available here.

Congratulations to Phil Newmark from the University of Illinois who was named HHMI Investigator! From the article:

According to those making the award, Newmark has been “instrumental in establishing planarians as a model system for studying regeneration at the molecular level. … (He) is exploring a central question that has long intrigued biologists – what are the signals or cues that tell a cell to become a germ cell? He hopes to answer that question by studying the ways planarians develop and regenerate their germ cells.”

“The department is delighted and proud of Dr. Newmark’s selection as an HHMI investigator,” said cell and developmental biology professor and department head Andrew Belmont. “The vast majority of scientists devote their careers to making steady but incremental progress on previously established lines of research. In contrast, a very select, very small group of scientists instead pioneer completely new approaches and methodologies, which then serve a much broader community. Dr. Newmark falls into the latter class of scientists, and it is tremendously satisfying to see the HHMI reward him for his vision, risk-taking and hard work,” Belmont said.

I have finally fixed the issue with the RSS feeds on this site. Feel free to email me if you notice any other problem.

Beta-Catenin Defines Head Versus Tail Identity During Planarian Regeneration and Homeostasis
Kyle A. Gurley, Jochen C. Rink, Alejandro Sánchez Alvarado*

After amputation, freshwater planarians properly regenerate a head or tail from the resulting anterior or posterior wound. The mechanisms that differentiate anterior from posterior and direct the replacement of the appropriate missing body parts are unknown. We found that in the planarian Schmidtea mediterranea, RNA interference (RNAi) of β-catenin or dishevelled causes the inappropriate regeneration of a head instead of a tail at posterior amputations...

Comparative analysis of septic injury-inducible genes in phylogenetically distant model organisms of regeneration and stem cell research, the planarian Schmidtea mediterranea and the cnidarian Hydra vulgaris

Boran Altincicek and Andreas Vilcinskas

"...We identified numerous immune-inducible genes in Hydra and Schmidtea that show a similar distribution corresponding to their physiological roles, although lineages of both animals split from their common ancestor for more than five hundred millions of years. The present study is the first analysis of immune-inducible genes of these two phylogenetically distant model organisms of regeneration and provide numerous candidate genes that we can use as a starting point for comparative examination of interrelationships between immunity and homeostasis."

Planarian GSK3s are involved in neural regeneration

Teresa Adell, Maria Marsal, Emili Saló

Glycogen synthase kinase-3 (GSK3) is a key element in several signaling cascades that is known to be involved in both patterning and neuronal organization. It is, therefore, a good candidate to play a role in neural regeneration in planarians. We report the characterization of three GSK3 genes in Schmidtea mediterranea. Phylogenetic analysis shows that Smed-GSK3.1 is highly conserved ...

Silencing of Smed-{beta}catenin1 generates radial-like hypercephalized planarians
Marta Iglesias, Jose Luis Gomez-Skarmeta, Emili Saló, and Teresa Adell*
* Author for correspondence (e-mail: tadellc@ub.edu)

Little is known about the molecular mechanisms responsible for axis establishment during non-embryonic processes such as regeneration and homeostasis. To address this issue, we set out to analyze the role of the canonical Wnt pathway in planarians, flatworms renowned for their extraordinary morphological plasticity. Canonical Wnt signalling is an evolutionarily conserved mechanism to confer polarity during embryonic development, specifying the anteroposterior (AP) axis in most bilaterians and the dorsoventral (DV) axis in early vertebrate embryos. {beta}-Catenin is a key element in this pathway, although it is a bifunctional protein that is also involved in cell-cell adhesion. Here, we report the characterization of two {beta}-catenin homologs from Schmidtea mediterranea (Smed-{beta}catenin1/2). Loss of function...

SmedGD: the Schmidtea mediterranea genome database

Sofia M.C. Robb, Eric Ross and Alejandro Sánchez Alvarado

The planarian Schmidtea mediterranea is rapidly emerging as a model organism for the study of regeneration, tissue homeostasis and stem cell biology. The recent sequencing, assembly and annotation of its genome are expected to further buoy the biomedical importance of this organism. In order to make the extensive data associated with the genome sequence accessible to the biomedical and planarian communities, we have created the Schmidtea mediterranea Genome Database (SmedGD). SmedGD integrates in a single web-accessible portal all available data associated with the planarian genome, including predicted and annotated genes, ESTs, protein homologies, gene expression patterns and RNAi phenotypes. Moreover, SmedGD was designed using tools provided by the Generic Model Organism Database (GMOD) project, thus making its data structure compatible with other model organism databases. Because of the unique phylogenetic position of planarians, SmedGD (http://smedgd.neuro.utah.edu) will prove useful not only to the planarian research community, but also to those engaged in developmental and evolutionary biology, comparative genomics, stem cell research and regeneration.

Scientists Study Flatworm Germ Cells

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University of Illinois developmental biology Professor Phillip Newmark and colleagues studying the planarian Schmidtea mediterranea have made a few discoveries related to genes called nanos, which were previously known to play a critical role in germ cell development in several other model organisms.

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From the "Innovations Report":

Study of planarians offers insight into germ cell development

Graduate student Yuying Wang and the other team members were able to show that nanos is essential for inductive specification in planarians. Blocking nanos expression by means of RNA interference immediately after the planarians hatched prevented the emergence and development of germ cells. Blocking nanos in mature adults caused their ovaries and testes to disappear. And when the researchers blocked nanos expression in planarians that had had their bodies and reproductive organs detached from their brains, the planarians regenerated new bodies, but with no reproductive cells.

Article Link from RNA Journal

MicroRNAs from the Planarian Schmidtea mediterranea: A model system for stem cell biology

Dasaradhi Palakodeti^1,, Magda Smielewska^1, and Brenton R. Graveley

Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030-3301, USA

MicroRNAs (miRNAs) are ~22-nt RNA molecules that typically bind to the 3' untranslated regions of target mRNAs and function to either induce mRNA degradation or repress translation. miRNAs have been shown to play important roles in the function of stem cells and cell lineage decisions in a variety of organisms, including humans. Planarians are bilaterally symmetric metazoans that have the unique ability to completely regenerate lost tissues or organs. This regenerative capacity is facilitated by a population of stem cells known as neoblasts. Planarians are therefore an excellent model system for studying many aspects of stem cell biology. Here we report the cloning and initial characterization of 71 miRNAs from the planarian Schmidtea mediterranea. While several of the S. mediterranea miRNAs are members of miRNA families identified in other species, we also identified a number of planarian-specific miRNAs. This work lays the foundation for functional studies aimed at addressing the role of these miRNAs in regeneration, cell lineage decisions, and basic stem cell biology.

Experiments With Planarian Worms Continue On The ISS