SMEDWI-2 Is a PIWI-Like Protein That Regulates Planarian Stem Cells

Reddien, Peter W.; Oviedo, Néstor J.; Jennings, Joya R.; Jenkin, James C.; Alvarado, Alejandro Sánchez

doi:10.1126/science.1116110

Cited by 573 publications

(850 citation statements)

References 18 publications

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“…Irradiation has long been known to specifically eliminate the only known mitotically active cells in planarians, i.e. the neoblasts (Bardeen and Baetjer, 1904;Dubois, 1949;Reddien et al, 2005b). We amputated irradiated animals parasagittally and examined expression of smedbmp4-1.…”

Section: Research Articlementioning

confidence: 99%

“…The D.21.6 gene is expressed in cells that reside around the entire periphery of the animal (Kato et al, 1999). D.21.6 expression was perturbed at the midline of cephalic and caudal blastemas of RNAi animals (smedolloid-1(RNAi): 9/10 cephalic and 9/10 caudal blastemas abnormal; smedsmad4-1(RNAi): 8/8 cephalic and 7/8 caudal blastemas abnormal; smedbmp4-1(RNAi): 3/10 cephalic and 10/10 caudal blastemas were abnormally dispersed in 4045 RESEARCH ARTICLE BMP signaling and planarian regeneration Following whole-mount in situ hybridization with a smedbmp4-1 riboprobe, animals were sectioned as previously described (Reddien et al, 2005b). In both panels, dorsal is to the right.…”

Section: Smedbmp4-1 Signaling Regulates Midline Tissue Formation In Smentioning

confidence: 99%

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BMP signaling regulates the dorsal planarian midline and is needed for asymmetric regeneration

et al. 2007

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Planarians can be cut into irregularly shaped fragments capable of regenerating new and complete organisms. Such regenerative capacities involve a robust ability to restore bilateral symmetry. We have identified three genes needed for bilaterally asymmetric fragments to regenerate missing body parts. These genes are candidate components of a signaling pathway that controls the dorsal-ventral patterning of many animal embryos: a BMP1/Tolloid-like gene (smedolloid-1), a SMAD4-like gene (smedsmad4-1), and a BMP2/4/DPP-like gene (smedbmp4-1). BMP signaling was involved in the formation of new tissues at the midline of regeneration, the dorsal-ventral patterning of new tissues, and the maintenance of the dorsal-ventral pattern of existing adult tissue in homeostasis. smedbmp4-1 was normally expressed at the dorsal midline. Asymmetric fragments lacking a midline displayed new smedbmp4-1 expression prior to formation of a regenerative outgrowth (blastema). Asymmetric fragments containing the midline displayed expanded smedbmp4-1 expression towards the wound. We suggest injured animals that lack left-right symmetry reset their midline through modulation of BMP activity as an early and necessary event in regeneration.

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Section: Research Articlementioning

confidence: 99%

Section: Smedbmp4-1 Signaling Regulates Midline Tissue Formation In Smentioning

confidence: 99%

BMP signaling regulates the dorsal planarian midline and is needed for asymmetric regeneration

et al. 2007

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“…PIWI proteins are essential for the biogenesis and function of piRNAs, and they appear to have undergone an expansion in the planarian genome. We have identified at least 7 likely planarian PIWI genes, of which 3 (SMEDWI-1-3) have been in part functionally characterized (9,10). For example, depletion of SMEDWI-2 has been shown to generate specific defects in stem-cell-mediated regeneration and homeostasis (9).…”

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confidence: 99%

“…We have identified at least 7 likely planarian PIWI genes, of which 3 (SMEDWI-1-3) have been in part functionally characterized (9,10). For example, depletion of SMEDWI-2 has been shown to generate specific defects in stem-cell-mediated regeneration and homeostasis (9). Because neoblasts can give rise to germ-line cells in planaria, it is perhaps not surprising that at least SMEDWI-1 and SMEDWI-2 proteins are specifically expressed in neoblasts, and that depletion of SMEDWI-2 or SMEDWI-3 reduces piRNA production and both are required for neoblast function and regeneration (10).…”

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High-resolution profiling and discovery of planarian small RNAs

Friedländer

Adamidi

Han

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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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. Sequencing, as well as quantitative PCR of small RNAs, uncovered 10 miRNAs enriched in planarian stem cells. These miRNAs are downregulated 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.microRNAs ͉ miRNAs ͉ piRNAs ͉ regeneration ͉ stem cells P lanarians have become a molecularly tractable model system in which to study regeneration, tissue homeostasis, and stem-cell biology (1). Planaria are free-living, triploblastic flatworms of the phylum Platyhelminthes, which is presently considered to belong to the superphylum Lophotrochozoa. Model systems for modern molecular and developmental biology have almost exclusively focused on the other 2 superphyla, i.e., the Deuterostomes (which includes vertebrates) and the Ecdysozoa (e.g., Caenorhabditis elegans and Drosophila melanogaster). Unlike these model systems, planarians possess remarkable regeneration abilities. Decapitation, for example, results in the complete regeneration of the head within 7 days after amputation. Such robust restoration of missing body parts is mediated by adult stem cells known as neoblasts (2). Of the thousands of known planarian species, Schmidtea mediterranea is arguably the species of choice for modern molecular biology and high-throughput, genome-wide approaches because it is diploid, it exists in sexual and asexual strains, and its genome has recently been sequenced and annotated (3). The size of its genome is roughly a third of the human genome, and Ϸ80% of the Ϸ20,000 annotated planarian genes have orthologs in humans. Moreover, by morphology alone, neoblasts and their immediate division progeny comprise Ϸ25% of all cells in the adult animal (4). In addition, RNAi screens have identified hundreds of genes specifically linked to planarian regeneration and stem-cell biology (5). Many of these genes are conserved in humans, and thus understanding planarian ...

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“…For example, work in two different species, Schmidtea mediterranea and Dugesia japonica, suggests that two genes, the Pumilio homologue Djpum and the bruno-like bruli are involved in neoblast maintainance but are not required for blastema formation [3,4]. In contrast, stem cell maintainance is not dependent on the Piwi homologue Smedwi-2; instead, this gene is required for the production of neoblast progeny [5]. Rossi et al also touch on their current efforts, combining of microarrays with knockdown approaches, which hold the promise of revealing novel aspects of stem cell biology.…”

Section: Introduction (Part Of a Multi-author Review)mentioning

confidence: 99%