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Planarian yorkie/YAP functions to integrate adult stem cell proliferation, organ homeostasis, and maintenance of axial patterning

ABSTRACT: During adult homeostasis and regeneration, the freshwater planarian must accomplish a constant balance between cell proliferation and cell death, while also maintaining proper tissue and organ size and patterning. Yet how these ordered processes are precisely modulated, remains relatively unknown. Here we show that planarians use the downstream effector of the Hippo signalling cascade, yorkie (yki; YAP in vertebrates) to control a diverse set of pleiotropic processes in organ homeostasis, stem cell regulation, regeneration, and axial patterning. We show that yki functions to maintain the homeostasis of the planarian excretory (protonephridial) system and to limit stem cell proliferation, while not affecting the differentiation process or cell death. Finally, we show that yki synergizes with WNT/β-catenin signalling to repress head determination by limiting the expression domains of posterior WNT genes and the WNT-inhibitor notum. Together, our data show that yki is a key factor in planarians that integrates stem cell proliferation control, organ homeostasis, and the spatial patterning of tissues.

ORGANISM(S): Schmidtea mediterranea

PROVIDER: GSE73700 | GEO | 2015/10/03

SECONDARY ACCESSION(S): PRJNA297689

REPOSITORIES: GEO

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Yorkie is required to restrict the injury responses in planarians

Project description:Regeneration requires the precise integration of cues that initiate proliferation, direct differentiation, and ultimately re-pattern tissues to the proper size and scale. Yet how these processes are integrated with wounding cues remains relatively unknown. The freshwater planarian, Schmidtea mediterranea, is an ideal model to study the stereotyped proliferative and transcriptional responses to injury due to its high capacity for regeneration. Here, we characterize the effector of the Hippo signalling cascade, yorkie, during planarian regeneration and its role in restricting early injury responses. In yki(RNAi) regenerating animals, wound responses are hyper-activated; the bimodal proliferation kinetics are heighted and prolonged, while the transcriptional injury responses are similarly augmented with dysregulated temporal patterns. We also uncovered novel wound-induced genes by RNAseq that are primarily associated with tissue patterning. Indeed, a high proportion of non-wound- and wound-induced patterning molecules are mis-expressed in yki(RNAi), which we demonstrate is in part due to an expanded muscle cell population. These altered injury responses have consequential effects on regenerative outcomes, specifically sensing the size of a given injury and appropriately scaling organ and tissue sizes. Taken together, our results suggest that yki functions as a key node to integrate the injury responses of proliferation, apoptosis, injury-induced transcription, and patterning to coordinate regeneration.

2017-06-20 | GSE97787 | GEO

454 Life Sciences/Roche and Illumina sequencing of small RNAs from planarian samples

Project description: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 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. Sequencing, as well as quantitative PCR of small RNAs uncovered ten miRNAs enriched in planarian stem cells. These miRNAs are down-regulated in animals in which stem cells have been abrogated by irradiation, and thus constitute miRNAs likely associated with specific stem cell functions. Altogether, we present the first comprehensive small RNA analysis in animals belonging to the third animal superphylum, the Lophotrochozoa, and single out a number of miRNAs that may function in regeneration. Several of these miRNAs are deeply conserved in animals. Small RNAs were sequenced from FACS-sorted neoblast stem cells, untreated planarians and irradiated planarians, depleted of neoblasts

2009-06-30 | E-GEOD-16159 | biostudies-arrayexpress

Schmidtea mediterranea

Project description:Planarian yorkie/YAP functions to integrate adult stem cell proliferation, organ homeostasis, and maintenance of axial patterning

| PRJNA297689 | ENA

HOX gene complement and expression in the planarian Schmidtea mediterranea

Project description:Background: Freshwater planarians are well known for their regenerative abilities. Less well known is how planarians maintain spatial patterning in long-lived adult animals or how they re-pattern tissues during regeneration. HOX genes are good candidates to regulate planarian spatial patterning, yet the full complement or genomic clustering of planarian HOX genes has not yet been described, primarily because only a few have been detectable by in situ hybridization, and none have given morphological phenotypes when knocked down by RNAi. Results: Because the planarian Schmidtea mediterranea (S. med) is unsegmented, appendage-less, and morphologically simple, it has been proposed that it may have a simplified HOX gene complement. Here we argue against this hypothesis and show that S. med has a total of 13 HOX genes, which represent homologs to all major axial categories, and can be detected by whole-mount in situ hybridization using a highly-sensitive method. In addition, we show that planarian HOX genes do not cluster in the genome, yet 5/13 have retained aspects of axially-restricted expression. Finally, we confirm HOX gene axial expression by RNA-deep-sequencing 6 anterior-to-posterior “zones” of the animal, which we provide as a dataset to the community to discover other axially-restricted transcripts. Conclusions: Freshwater planarians have an unappreciated HOX gene complexity, with all major axial categories represented. However, we conclude based on adult expression patterns that planarians have a derived body plan and their asexual lifestyle may have allowed for large changes in HOX expression from the last common ancestor between arthropods, flatworms, and vertebrates. Using our in situ method and axial zone RNAseq data, it should be possible to further understand the pathways that pattern the anterior-posterior axis of adult planarians.

2016-03-08 | GSE78937 | GEO

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2020-11-18 | PXD014628 | Pride

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