The head-regeneration transcriptome of the planarian Schmidtea mediterranea

Sandmann, Thomas; Vogg, Matthias Christian; Owlarn, Suthira; Boutros, Michael; Bartscherer, Kerstin

doi:10.1186/gb-2011-12-8-r76

Cited by 119 publications

(149 citation statements)

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“…In contrast to the existence of three Pitx gene family members (Pitx1-3) in vertebrates (Gage et al, 1999), we found only a single pitx gene in the genome (Cantarel et al, 2008) and different transcriptomes of S. mediterranea (Abril et al, 2010; Adamidi et al, 2011; Blythe et al, 2010;Sandmann et al, 2011). In silico translation of the mRNA sequence and subsequent protein alignment showed that the homeobox is highly conserved between planarian Pitx and the Pitx proteins from other species (supplementary material Fig.…”

Section: Smed-pitx Is Expressed In Mature Serotonergic Neuronscontrasting

confidence: 70%

A Pitx transcription factor controls the establishment and maintenance of the serotonergic lineage in planarians

2013

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In contrast to adult vertebrates, which have limited capacities for neurogenesis, adult planarians undergo constitutive cellular turnover during homeostasis and are even able to regenerate a whole brain after decapitation. This enormous plasticity derives from pluripotent stem cells residing in the planarian body in large numbers. It is still obscure how these stem cells are programmed for differentiation into specific cell lineages and how lineage identity is maintained. Here we identify a Pitx transcription factor of crucial importance for planarian regeneration. In addition to patterning defects that are co-dependent on the LIM homeobox transcription factor gene islet1, which is expressed with pitx at anterior and posterior regeneration poles, RNAi against pitx results in islet1-independent specific loss of serotonergic (SN) neurons during regeneration. Besides its expression in terminally differentiated SN neurons we found pitx in stem cell progeny committed to the SN fate. Also, intact pitx RNAi animals gradually lose SN markers, a phenotype that depends neither on increased apoptosis nor on stem cell-based turnover or transdifferentiation into other neurons. We propose that pitx is a terminal selector gene for SN neurons in planarians that controls not only their maturation but also their identity by regulating the expression of the Serotonin production and transport machinery. Finally, we made use of this function of pitx and compared the transcriptomes of regenerating planarians with and without functional SN neurons, identifying at least three new neuronal targets of Pitx.KEY WORDS: Planaria, Schmidtea mediterranea, Regeneration, Serotonergic neuron, Pitx, Islet1, Stem cell differentiation INTRODUCTIONTranscription factors are key regulators of differentiation processes and the misexpression of a small number of transcription factors can change the fate of a cell completely (reviewed by Sancho-Martinez et al., 2012). The family of paired class homeobox/pituitary homeobox (Pitx) transcription factors has been implicated in a number of differentiation decisions in mammals. For instance, Pitx proteins can act as terminal selectors, which are transcription factors that regulate both the terminal differentiation of a late progenitor cell and the establishment and maintenance of its cell type-specific functions (reviewed by Flames and Hobert, 2011;Hobert, 2011; RESEARCH ARTICLE STEM CELLS AND REGENERATIONMax Planck Research Group Stem Cells and Regeneration, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Strasse 54, 48149 Münster, Germany.*Author for correspondence (kerstin.bartscherer@mpi-muenster.mpg.de) This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.Received 20 February 2013; Accepted 22 August 2013 Hobert et al., 2010). In the mouse, Pitx2 and Pitx3 ar...

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Section: Smed-pitx Is Expressed In Mature Serotonergic Neuronscontrasting

confidence: 70%

A Pitx transcription factor controls the establishment and maintenance of the serotonergic lineage in planarians

2013

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“…However, only a subset of neoblasts in wounded planarians (neoblasts near wounds) express runt-1, demonstrating that injury induces gene expression heterogeneity in the neoblasts. runt-1 is required for normal eye regeneration (Sandmann et al, 2011;Wenemoser et al, 2012) and for the presence of sp6-9 + optic cup progenitor trails (Wenemoser et al, 2012). runt-1 does not display any expression specificity for particular regenerative contexts, but is generically induced by many or all injuries.…”

Section: Specialized Neoblasts Exist In Unamputated Animalsmentioning

confidence: 99%

“…The transcription factor runt-1 is rapidly induced (within 3 hours following amputation) at planarian wounds (Sandmann et al, 2011;Wenemoser et al, 2012), and expression is within neoblasts (Wenemoser et al, 2012). However, only a subset of neoblasts in wounded planarians (neoblasts near wounds) express runt-1, demonstrating that injury induces gene expression heterogeneity in the neoblasts.…”

Section: Specialized Neoblasts Exist In Unamputated Animalsmentioning

confidence: 99%

Specialized progenitors and regeneration

Reddien

2013

Development

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SummaryPlanarians are flatworms capable of regenerating all body parts. Planarian regeneration requires neoblasts, a population of dividing cells that has been studied for over a century. Neoblast progeny generate new cells of blastemas, which are the regenerative outgrowths at wounds. If the neoblasts comprise a uniform population of cells during regeneration (e.g. they are all uncommitted and pluripotent), then specialization of new cell types should occur in multipotent, non-dividing neoblast progeny cells. By contrast, recent data indicate that some neoblasts express lineage-specific transcription factors during regeneration and in uninjured animals. These observations raise the possibility that an important early step in planarian regeneration is the specialization of neoblasts to produce specified rather than naïve blastema cells.

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“…Thus, tag mapping in the present N and IR DGE libraries is currently incomplete but will improve as the reference genome becomes more annotated. Although it is undeniable that tag matching will augment with the novel whole transcriptome datasets described in (Abril et al, 2010;Blythe et al, 2010;Adamidi et al, 2011) as they become coordinated (Sandmann et al, 2011), and as genome annotation improves, the present analysis is focused on mapping against the previous classic ESTs and mRNAs NCBI deposited banks. First, at least 1065 of these sequences have been assessed in gene silencing experiments (Reddien et al, 2005).…”

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confidence: 99%

Global irradiation effects, stem cell genes and rare transcripts in the planarian transcriptome

Galloni¹

2012

Int. J. Dev. Biol.

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Stem cells are the closest relatives of the totipotent primordial cell, which is able to spawn millions of daughter cells and hundreds of cell types in multicellular organisms. Stem cells are involved in tissue homeostasis and regeneration, and may play a major role in cancer development. Among animals, planarians host a model stem cell type, called the neoblast, which essentially confers immortality. Gaining insights into the global transcriptional landscape of these exceptional cells takes an unprecedented turn with the advent of Next Generation Sequencing methods. Two Digital Gene Expression transcriptomes of Schmidtea mediterranea planarians, with or without neoblasts lost through irradiation, were produced and analyzed. Twenty one bp NlaIII tags were mapped to transcripts in the Schmidtea and Dugesia taxids. Differential representation of tags in normal versus irradiated animals reflects differential gene expression. Canonical and non-canonical tags were included in the analysis, and comparative studies with human orthologs were conducted. Transcripts fell into 3 categories: invariant (including housekeeping genes), absent in irradiated animals (potential neoblast-specific genes, IRDOWN) and induced in irradiated animals (potential cellular stress response, IRUP). Different mRNA variants and gene family members were recovered. In the IRDOWN class, almost all of the neoblast-specific genes previously described were found. In irradiated animals, a larger number of genes were induced rather than lost. A significant fraction of IRUP genes behaved as if transcript versions of different lengths were produced. Several novel potential neoblast-specific genes have been identified that varied in relative abundance, including highly conserved as well as novel proteins without predicted orthologs. Evidence for a large body of antisense transcripts, for example regulated antisense for the Smed-piwil1 gene, and evidence for RNA shortening in irradiated animals is presented. Novel neoblast-specific candidates include a peroxiredoxin protein that appears to be preferentially expressed in human embryonic stem cells.

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The head-regeneration transcriptome of the planarian Schmidtea mediterranea

Cited by 119 publications

References 59 publications

A Pitx transcription factor controls the establishment and maintenance of the serotonergic lineage in planarians

A Pitx transcription factor controls the establishment and maintenance of the serotonergic lineage in planarians

Specialized progenitors and regeneration

Global irradiation effects, stem cell genes and rare transcripts in the planarian transcriptome

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