Planarian Biology

A Dual Platform Approach to Transcript Discovery for the Planarian Schmidtea Mediterranea to Establish RNAseq for Stem Cell and Regeneration Biology

2010-12-20T14:17:00.001-06:00

Martin J. Blythe, Damian Kao, Sunir Malla, Joanna Rowsell, Ray Wilson, Deborah Evans, Jamie Jowett, Amy Hall, Virginie Lemay, Sabrina Lam, A. Aziz Aboobaker

The use of planarians as a model system is expanding and the mechanisms that control planarian regeneration are being elucidated. The planarian Schmidtea mediterranea in particular has become a species of choice. Currently the planarian research community has access to this whole genome sequencing project and over 70,000 expressed sequence tags. However, the establishment of massively parallel sequencing technologies has provided the opportunity to define genetic content, and in particular transcriptomes, in unprecedented detail. Here we apply this approach to the planarian model system. We have sequenced, mapped and assembled 581,365 long and 507,719,814 short reads from RNA of intact and mixed stages of the first 7 days of planarian regeneration. We used an iterative mapping approach to identify and define de novo splice sites with short reads and increase confidence in our transcript predictions. We more than double the number of transcripts currently defined by publicly available ESTs, resulting in a collection of 25,053 transcripts described by combining platforms. We also demonstrate the utility of this collection for an RNAseq approach to identify potential transcripts that are enriched in neoblast stem cells and their progeny by comparing transcriptome wide expression levels between irradiated and intact planarians. Our experiments have defined an extensive planarian transcriptome that can be used as a template for RNAseq and can also help to annotate the S. mediterranea genome. We anticipate that suites of other 'omic approaches will also be facilitated by building on this comprehensive data set including RNAseq across many planarian regenerative stages, scenarios, tissues and phenotypes generated by RNAi.

Full article here.

Genome-Wide Analyses Reveal a Role for Peptide Hormones in Planarian Germline Development

2010-10-28T17:28:00.003-05:00

Collins, J., Hou, X., Romanova, E., Lambrus, B., Miller, C., Saberi, A., Sweedler, J., Newmark, P.

Bioactive peptides (i.e., neuropeptides or peptide hormones) represent the largest class of cell-cell signaling molecules in metazoans and are potent regulators of neural and physiological function. In vertebrates, peptide hormones play an integral role in endocrine signaling between the brain and the gonads that controls reproductive development, yet few of these molecules have been shown to influence reproductive development in invertebrates. Here, we define a role for peptide hormones in controlling reproductive physiology of the model flatworm, the planarian Schmidtea mediterranea. Based on our observation that defective neuropeptide processing results in defects in reproductive system development, we employed peptidomic and functional genomic approaches to characterize the planarian peptide hormone complement, identifying 51 prohormone genes and validating 142 peptides biochemically. Comprehensive in situ hybridization analyses of prohormone gene expression revealed the unanticipated complexity of the flatworm nervous system and identified a prohormone specifically expressed in the nervous system of sexually reproducing planarians. We show that this member of the neuropeptide Y superfamily is required for the maintenance of mature reproductive organs and differentiated germ cells in the testes. Additionally, comparative analyses of our biochemically validated prohormones with the genomes of the parasitic flatworms Schistosoma mansoni and Schistosoma japonicum identified new schistosome prohormones and validated half of all predicted peptide-encoding genes in these parasites. These studies describe the peptide hormone complement of a flatworm on a genome-wide scale and reveal a previously uncharacterized role for peptide hormones in flatworm reproduction. Furthermore, they suggest new opportunities for using planarians as free-living models for understanding the reproductive biology of flatworm parasites.

Full article.

Schmidtea mediterranea: a model system for analysis of motile cilia.

2010-05-02T12:44:00.002-05:00

Rompolas P, Patel-King RS, King SM.

Cilia are cellular organelles that appeared early in the evolution of eukaryotes. These structures and the pool of about 600genes involved in their assembly and function are highly conserved in organisms as distant as single-cell protists, like Chlamydomonas reinhardtti, and humans (Silflow and Lefebvre, 2001). A significant body of work on the biology of cilia has been produced over the years, with the help of powerful model organisms including C. reinhardtti, Caenorhabditis elegans, sea urchins, and mice. However, specific limitations of these systems, especially regarding the ability to efficiently study gene loss-of-function, warrant the search for a new model organism to study cilia and cilia-based motility. Schmidtea mediterranea is a species of planarian (Class: Tubellaria) with a well-defined monostratified ciliated epithelium, which contributes to the motility of the organism, in addition to other more specialized ciliary structures. The use of S. mediterranea as an experimental system to study stem cell biology and regeneration has led to a recently sequenced genome and to the development of a wide array of powerful tools including the ability to inhibit gene expression via RNA interference. In addition, we have developed and describe here a number of methods for analyzing motile cilia in S. mediterranea. Overall, S. mediterranea is a highly versatile, easy to maintain, and genetically tractable organism that provides a powerful alternative model system for the study of motile cilia.

Article link

smed-prep

2010-05-02T12:33:00.001-05:00

This blog has moved

2010-04-23T07:08:00.001-05:00

This blog is now located at http://planarianbiology.blogspot.com/.
You will be automatically redirected in 30 seconds, or you may click here.

For feed subscribers, please update your feed subscriptions to
http://planarianbiology.blogspot.com/feeds/posts/default.

The TALE Class Homeobox Gene Smed-prep Defines the Anterior Compartment for Head Regeneration

2010-04-23T07:05:00.002-05:00

Daniel A. Felix, A. Aziz Aboobake

Planaria continue to blossom as a model system for understanding all aspects of regeneration. They provide an opportunity to understand how the replacement of missing tissues from preexisting adult tissue is orchestrated at the molecular level. When amputated along any plane, planaria are capable of regenerating all missing tissue and rescaling all structures to the new size of the animal. Recently, rapid progress has been made in understanding the developmental pathways that control planarian regeneration. In particular Wnt/beta-catenin signaling is central in promoting posterior fates and inhibiting anterior identity. Currently the mechanisms that actively promote anterior identity remain unknown. Here, Smed-prep, encoding a TALE class homeodomain, is described as the first gene necessary for correct anterior fate and patterning during planarian regeneration. Smed-prep is expressed at high levels in the anterior portion of whole animals, and Smed-prep(RNAi) leads to loss of the whole brain during anterior regeneration, but not during lateral regeneration or homeostasis in intact worms. Expression of markers of different anterior fated cells are greatly reduced or lost in Smed-prep(RNAi) animals. We find . . .

Full article here.

Germ layer specification and axial patterning in the embryonic development of the freshwater planarian Schmidtea polychroa

2010-02-15T10:19:00.000-06:00

José María Martín-Durána, Enrique Amayab and Rafael Romero.

Although patterning during regeneration in adult planarians has been studied extensively, very little is known about how the initial planarian body plan arises during embryogenesis. Herein, we analyze the process of embryo patterning in the species Schmidtea polychroa by comparing the expression of genes involved in the establishment of the metazoan body plan. Planarians present a derived ectolecithic spiralian development characterized by dispersed cleavage within a yolk syncytium and an early transient embryo capable of feeding on the maternally supplied yolk cells. During this stage of development, we only found evidence of canonical Wnt pathway, mostly associated with the development of its transient pharynx. At these stages, genes involved in gastrulation (snail) and germ layer determination (foxA and twist) are . . .

Full article here.

Autophagy and apoptosis in planarians

2010-01-24T04:44:00.002-06:00

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.

2010-01-19T08:44:00.001-06:00

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

2010-01-19T08:42:00.001-06:00

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

2009-12-26T08:22:00.001-06:00

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

2009-09-14T18:44:00.002-05:00

. . . 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. . .

Read the rest here.

2009-07-01T06:24:00.001-05:00

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 . . .

2009-06-25T07:29:00.002-05:00

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

2008-10-24T18:04:00.002-05:00

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

2008-10-24T17:57:00.001-05:00

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.

2008-05-28T17:39:00.003-05:00

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.

2008-04-28T07:23:00.004-05:00

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

2008-04-28T07:17:00.001-05:00

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...

2008-04-27T19:59:00.000-05:00

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."

2008-04-01T21:31:00.001-05:00

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 ...

2008-03-24T18:45:00.003-05:00

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...

2007-11-07T10:14:00.000-06:00

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.

2007-04-27T12:27:00.000-05:00

Scientists Study Flatworm Germ Cells

...

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.

...

2007-04-24T07:12:00.000-05:00

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.

2006-12-10T07:37:00.000-06:00

Article Link from RNA Journal

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

Dasaradhi Palakodeti¹^,, Magda Smielewska¹^, 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 bindto the 3' untranslated regions of target mRNAs and functionto either induce mRNA degradation or repress translation. miRNAshave been shown to play important roles in the function of stemcells and cell lineage decisions in a variety of organisms,including humans. Planarians are bilaterally symmetric metazoansthat have the unique ability to completely regenerate lost tissuesor organs. This regenerative capacity is facilitated by a populationof stem cells known as neoblasts. Planarians are therefore anexcellent model system for studying many aspects of stem cellbiology. Here we report the cloning and initial characterizationof 71 miRNAs from the planarian Schmidtea mediterranea. Whileseveral of the S. mediterranea miRNAs are members of miRNA familiesidentified in other species, we also identified a number ofplanarian-specific miRNAs. This work lays the foundation forfunctional studies aimed at addressing the role of these miRNAsin regeneration, cell lineage decisions, and basic stem cellbiology.

2006-09-25T07:20:00.000-05:00

Experiments With Planarian Worms Continue On The ISS

2006-09-11T23:44:00.000-05:00

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

Dasaradhi Palakodeti1,, Magda Smielewska1, and Brenton R. Graveley

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.

2006-08-17T15:16:00.000-05:00

Critical stem cell protein identified

2006-08-11T11:46:00.000-05:00

Worm could aid study of human stem cells

2006-08-09T10:08:00.000-05:00

From News-Medical.net:
Scientists identify gene involved in stem cell self-renewal in planaria

From the Philadelphia Inquirer:
Regenerating worm may give insight into how stem cells work

2006-08-07T19:16:00.000-05:00

The St. Louis Post Dispatch has two stories on the recent publication from the Newmark Laboratory.
Scientists discover stem-cell answer to how worms regenerate
Worm could aid study of human stem cells

The National Science Foundation has issued a press-release as well.
Flatworms at Forefront of Regeneration Research

2006-08-07T12:45:00.000-05:00

Developmental Cell published a paper on bruno-like protein being involved in stem cell maintenance. The abstract is available here.

Tingxia Guo, Antoine H.F.M. Peters and Phillip A. Newmark

Abstract:
The regenerative abilities of freshwater planarians are based on neoblasts, stem cells maintained throughout the animal's life. We show that a member of the Bruno-like family of RNA binding proteins is critical for regulating neoblasts in the planarian Schmidtea mediterranea. Smed-bruno-like (bruli) mRNA and protein are expressed in neoblasts and the central nervous system. Following bruli RNAi, which eliminates detectable Bruli protein, planarians initiate the proliferative response to amputation and form small blastemas but then undergo tissue regression and lysis. We characterize the neoblast population by using antibodies recognizing SMEDWI-1 and Histone H4 (monomethyl-K20) and cell-cycle markers to label subsets of neoblasts and their progeny. bruli knockdown results in a dramatic reduction/elimination of neoblasts. Our analyses indicate that neoblasts lacking Bruli can respond to wound stimuli and generate progeny that can form blastemas and differentiate; yet, they are unable to self-renew. These results suggest that Bruli is required for stem cell maintenance.

2006-07-30T08:23:00.000-05:00

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

2006-01-25T21:19:00.000-06:00

Alejandro Sanchez Alvarado's commentary "The freshwater planarian Schmidtea mediterranea: embryogenesis, stem cells and regeneration" has been posted to the web.

Abstract:
Planarians have been used as a model to study development and
regeneration for more than 200 years. Research on these animals
has traditionally focused on surgical and pharmacological
manipulations. Recently, the dissection of planarians has
become more molecular in nature. The isolation of thousands of
expressed sequence tags and the introduction of in situ
hybridizations, immunocytology, and RNA-mediated gene
interference has opened the door to gene discovery and to the
study of gene function in planarians during development and
regeneration. These advances promise to shed mechanistic
insight into basic biological attributes such as regeneration and
stem-cell regulation.

2006-01-21T23:27:00.000-06:00

A poster featuring planarian biology won a science competition (archive) at UIUC. ;-)

Image
Peter Zavislak
Analysis of human disease homologues in
Schmidtea mediterranea by in situ hybridization and RNAi

2006-01-09T07:46:00.000-06:00

The Washington University Genome Sequencing Center has a short description of the biology, habitat, and sequencing summary of Schmidtea mediterranea.

2005-12-14T10:30:00.000-06:00

The EST-database analysis abstract in the recent PNAS is available:

The planarian Schmidtea mediterranea as a model for epigenetic germ cell specification: Analysis of ESTs from the hermaphroditic strain

Abstract:
Freshwater planarians have prodigious regenerative abilities that enable them to form complete organisms from tiny body fragments. This plasticity is also exhibited by the planarian germ cell lineage. Unlike many model organisms in which germ cells are specified by localized determinants, planarian germ cells appear to be specified epigenetically, arising postembryonically from stem cells. The planarian Schmidtea mediterranea is well suited for investigating the mechanisms underlying epigenetic germ cell specification. Two strains of S. mediterranea exist: a hermaphroditic strain that reproduces sexually and an asexual strain that reproduces by means of transverse fission. To date, expressed sequence tags (ESTs) have been generated only from the asexual strain. To develop molecular reagents for studying epigenetic germ cell specification, we have sequenced 27,161 ESTs from two developmental stages of the hermaphroditic strain of S. mediterranea; this collection of ESTs represents ~10,000 unique transcripts. BLAST analysis of the assembled ESTs showed that 66% share similarity to sequences in public databases. We annotated the assembled ESTs using Gene Ontology terms as well as conserved protein domains and organized them in a relational database. To validate experimentally the Gene Ontology annotations, we used whole-mount in situ hybridization to examine the expression patterns of transcripts assigned to the biological process "reproduction." Of the 53 genes in this category, 87% were expressed in the reproductive organs. In addition to its utility for studying germ cell development, this EST collection will be an important resource for annotating the planarian genome and studying this animal's amazing regenerative abilities.

2005-12-13T15:58:00.000-06:00

There are two recent news stories about research in Dr. Newmark's lab at the University of Illinois:

Flatworm genes may provide insights into human diseases, researchers say

"One of the striking things we found is that when we look at planarian genes, we see a group that is conserved between planarians and mammals that is not found in Drosophila or C. elegans," said Phillip A. Newmark, a professor of cell and developmental biology at Illinois.

and

Flatworm genes used for human ills studies

Not only were 66 percent of them similar to sequences already in public databases, the researchers found 142 of 287 genes associated with human diseases. Since the ESTs they studied represent only about one-half of the total, 'it seems likely that the vast majority of human disease genes will have homologues in planarians,' the scientists concluded.

2005-11-28T11:57:00.000-06:00

The Scientist has a news story about smedwi-2. Adult stem cell regulator?

The article has quite a bit more information than in previous stories:

Inhibiting smedwi-2 did not knock out neoblasts, however. Fluorescence-activated cell sorting analyses indicated neoblasts remained present in smedwi-2-silenced planarians, and in situ hybridization showed some neoblasts expressed cell division marker cyclinB, demonstrating they were still proliferating.

However, after inhibiting smedwi-2 with RNAi, the researchers saw that bromodeoxyuridine-labeled neoblasts entered the epidermis sooner than normal and were grossly misshapen. This suggests that smedwi-2 ensures that dividing neoblasts generate progeny that can replace cells during homeostasis and missing tissues during regeneration, they report.

and:

Phil Newmark at the University of Illinois at Urbana-Champaign is currently developing antibodies against planarian PIWI members, Sanchez Alvarado noted, which could help reveal where smedwi-2 is localized within the cell and how it works, perhaps through interacting with RNAs. "SMEDWI-2 does have PAZ and PIWI domains, which are known to bind small RNAs such as siRNAs and cleave mRNAs, respectively," Sanchez Alvarado said.

2005-11-27T09:29:00.000-06:00

The smedwi-2 discovery has made its way to Slashdot.

University of Utah Press Release

2005-11-24T15:12:00.000-06:00

Eurekalert has posted a news release which talks about how silencing the smedwi-2 gene in Schmidtea mediterranea causes a phenotype similar to that encountered when destroying the neoblast population by X-irradiation. The (surprising) result is likely due to disruption of adult stem cell terminal differentiation, which would cause problems in homeostasis and lead to death. Alvarado and Reddien's research is presented in the November 25th edition of Science.

Silenced gene in worm shows role in regeneration

ScienceDaily has posted a similar news story:
Silenced Gene In Worm Shows Role In Regeneration

2005-11-15T11:04:00.000-06:00

Eurekalert reports Dr. Levin's lab at the Forsyth Institute showed that gap junctions play a critical role in communication of tissues during regeneration. Knocking out gap junction function causes regeneration defects including multiple heads. The paper is published in the November 15th edition of Developmental Cell.

New understanding of regeneration gained by Forsyth scientists

2005-11-08T12:43:00.000-06:00

Newswire has a short piece on planarians and their use in developmental biology.
New Tools for an Old Can of Worms

2005-10-25T17:55:00.000-05:00

Important articles in planarian biology:

Zayas and Newmark paper on spliced leader trans-splicing in freshwater planarians.

Ingestion of bacterially expressed double-stranded RNA inhibits gene expression in planarians.

Allometric scaling and proportion regulation in the freshwater planarian Schmidtea mediterranea

The Schmidtea mediterranea database as a molecular resource for studying platyhelminthes, stem cells and regeneration.

Not your father’s planarian: a classic model enters the era of functional genomics.

Regeneration in planaria.

Bromodeoxyuridine specifically labels the regenerative stem cells of planarians.

Double-stranded RNA specifically disrupts gene expression during planarian regeneration.

2005-10-23T17:36:00.000-05:00

Cebria et al Paper on Netrin Role in Neuroregeneration

2005-10-23T17:00:00.000-05:00

White Paper for a Planarian Genome Project

The proposal for the sequencing of the planarian Schmidtea mediterranea has been made available at the Washington University Genome Sequencing Center website. The planarian genome project proposal can be read here. [PDF-format]