Les Planàries d'aigües dolces a Catalunya i les illes Balears. I. Clau sistemàtica i distribució geogràfica

The geographical distribution of freshwater planarians in Catalonia and the Balearic Islands has been studied from old and new records. Up to now, seven species have been found in Catalonia throughout the 44 localities studied, whereas only three species are present in the 13 localities studied in the Balearic Islands. The species and the geographical pattern found are similar to the published European records. The criteria for a correct diagnosis of planarian species are assessed especially when dealing with complex groups like the subgenera Schmidtea and the old «gonocephala» group. We stress the need to study the karyotypes to diagnose correctly some of the present species and to discover new races and species hidden under a similar external appearance. Taking into account these considerations a key is provided to assist clasification of these organisms. Finally, a pledge is made to stimulate the flow of sound information to add in a future work

Organizing the DV axis during planarian regeneration

During regeneration, lost structures are rebuilt and perfectly integrated within the remaining non-injured tissues. This fascinating process captured the attention of one of the founders of modern genetics, T. H. Morgan. He was particularly interested in understanding regeneration in freshwater planarians, which can regenerate a whole animal from a small piece of their bodies. He performed numerous experiments to understand how polarity is re-established such that an anterior-facing wound regenerates a head whereas a posterior-facing wound regenerates a tail. However, it has not been until more than 100 years later that the molecules required to determine axial polarity have been identified. Several studies have now shown that the Wnt/β-catenin and Hedgehog pathways are required for anteroposterior axis specification, whereas the establishment of the planarian dorsoventral (DV) axis relies on the Bone Morphogenetic Protein (BMP) pathway. Two recent papers have now uncovered additional conserved (anti-dorsalizing morphogenetic protein) and novel (noggin-like genes) elements that regulate planarian DV axis regeneration. Here, we summarize those results and present new data and hypotheses to explain the role that noggin-like genes might play

Gtdap-1 and the role of autophagy during planarian regeneration and starvation

Planarians have been established as an ideal model organism for stem cell research and regeneration. Planarian regeneration and homeostasis require an exquisite balancing act between cell death and cell proliferation as new tissues are made (epimorphosis) and existing tissues remodeled (morphallaxis). Some of the genes and mechanisms that control cell proliferation and pattern formation are known. However, studies about cell death during remodeling are few and far between. We have studied the gene Gtdap-1, the planarian ortholog of human death-associated protein-1 or DAP-1. DAP-1 together with DAP-kinase has been identified as a positive mediator of programmed cell death induced by gamma-interferon in HeLa cells. We have found that the gene functions at the interface between autophagy and cell death in the remodeling of the organism that occurs during regeneration and starvation in sexual and asexual races of planarians. Our data suggest that autophagy of existing cells may be essential to fuel the continued proliferation and differentiation of stem cells by providing the necessary energy and building blocks to neoblasts

The pioneer factor Smed-gata456-1 is required for gut cell differentiation and maintenance in planarians

How adult stem cells differentiate into different cell types remains one of the most intriguing questions in regenerative medicine. Pioneer factors are transcription factors that can bind to and open chromatin, and are among the first elements involved in cell differentiation. We used the freshwater planarian Schmidtea mediterranea as a model system to study the role of the gata456 family of pioneer factors in gut cell differentiation during both regeneration and maintenance of the digestive system. Our findings reveal the presence of two members of the gata456 family in the Schmidtea mediterranea genome; Smed-gata456-1 and Smed-gata456-2. Our results show that Smed-gata456-1 is the only ortholog with a gut cell-related function. Smed-gata456-1 is essential for the differentiation of precursors into intestinal cells and for the survival of these differentiated cells, indicating a key role in gut regeneration and maintenance. Furthermore, tissues other than the gut appear normal following Smed-gata456-1 RNA interference (RNAi), indicating a gut-specific function. Importantly, different neoblast subtypes are unaffected by Smed-gata456-1(RNAi), suggesting that 1) Smed-gata456-1 is involved in the differentiation and maintenance, but not in the early determination, of gut cells; and 2) that the stem cell compartment is not dependent on a functional gut

Planarians as a model to assess in vivo the role of matrix metalloproteinase genes during homeostasis and regeneration

Matrix metalloproteinases (MMPs) are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2) are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB) are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi) during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi). Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues. These results have high potential to generate significant information for development of regenerative and anti cancer therapies

Digital Gene Expression approach over multiple RNA-Seq data sets to detect neoblast transcriptional changes in Schmidtea mediterranea

The freshwater planarian Schmidtea mediterranea is recognised as a valuable model for research into adult stem cells and regeneration. With the advent of the high-throughput sequencing technologies, it has become feasible to undertake detailed transcriptional analysis of its unique stem cell population, the neoblasts. Nonetheless, a reliable reference for this type of studies is still lacking. Taking advantage of digital gene expression (DGE) sequencing technology we compare all the available transcriptomes for S. mediterranea and improve their annotation. These results are accessible via web for the community of researchers. Using the quantitative nature of DGE, we describe the transcriptional profile of neoblasts and present 42 new neoblast genes, including several cancer-related genes and transcription factors. Furthermore, we describe in detail the Smed-meis-like gene and the three Nuclear Factor Y subunits Smed-nf-YA, Smed-nf-YB-2 and Smed-nf-YC. DGE is a valuable tool for gene discovery, quantification and annotation. The application of DGE in S. mediterranea confirms the planarian stem cells or neoblasts as a complex population of pluripotent and multipotent cells regulated by a mixture of transcription factors and cancer-related genes

La regeneració i l'homeòstasi en les planàries, un model clàssic de biologia del desenvolupament

La regeneració és la capacitat d'un organisme de reemplaçar fragments perduts a causa d'una amputació traumàtica o degeneració. La regeneració de les noves estructures té lloc bé a partir de proliferació cel·lular i formació de novo, bé per remodelació dels teixits preexistents. Les planàries poden regenerar un nou organisme sencer a partir de petits fragments del seu cos. Aquest fet ha atret l'interès dels científics al llarg de la història. El 1814, Dalyell conclou que les planàries «es poden considerar immortals sota la fulla d'una navalla». La regeneració en les planàries requereix la generació de teixit nou en el lloc de la ferida mitjançant proliferació cel·lular, que produeix un teixit nou indiferenciat, el blastema, i el remodelatge dels teixits preexistents per recuperar les proporcions del nou organisme regenerat. Una altra propietat espectacular de les planàries és la capacitat de créixer i decréixer segons la ingesta d'aliment. En tot moment, però, al llarg d'aquest creixement/decreixement es mantenen les proporcions corporals i funcions correctes, gràcies al control homeostàtic. Tota aquesta plasticitat és deguda, a escala cel·lular, a la presència de cèl·lules mare totipotents en un alt percentatge (entre el 20-30 % del total cel·lular en un organisme adult). Una altra propietat fonamental és la contínua activitat dels mecanismes morfogenètics, que normalment apareixen una sola vegada en el desenvolupament de la resta dels altres organismes. L'aplicació de noves metodologies a escala cel·lular, molecular i genètica en l'era postgenòmica ens ha permès estudiar funcionalment vies i gens del desenvolupament en un nou escenari, la regeneració de planàries

Analysis of Fox genes in Schmidtea mediterranea reveals new families and a conserved role of Smed‑foxO in controlling cell death

The forkhead box (Fox) genes encode transcription factors that control several key aspects of development. Present in the ancestor of all eukaryotes, Fox genes underwent several duplications followed by loss and diversification events that gave rise to the current 25 families. However, few Fox members have been identified from the Lophotrochozoa clade, and specifically from planarians, which are a unique model for understanding development, due to the striking plasticity of the adult. The aim of this study was to identify and perform evolutionary and functional studies of the Fox genes of lophotrochozoan species and, specifically, of the planarian Schmidtea mediterranea. Generating a pipeline for identifying Forkhead domains and using phylogenetics allowed us the phylogenetic reconstruction of Fox genes. We corrected the annotation for misannotated genes and uncovered a new family, the QD, present in all metazoans. According to the new phylogeny, the 27 Fox genes found in Schmidtea mediterranea were classified into 12 families. In Platyhelminthes, family losses were accompanied by extensive gene diversification and the appearance of specific families, the A(P) and N(P). Among the newly identified planarian Fox genes, we found a single copy of foxO, which shows an evolutionary conserved role in controlling cell death

FoxK1 is required for ectodermal cell differentiation during planarian regeneration

Forkhead box (Fox) genes belong to the 'winged helix' transcription factor superfamily. The function of some Fox genes is well known, such as the role of foxO in controlling metabolism and longevity and foxA in controlling differentiation of endodermal tissues. However, the role of some Fox factors is not yet well characterized. Such is the case of FoxK genes, which are mainly studied in mammals and have been implicated in diverse processes including cell proliferation, tissue differentiation and carcinogenesis. Planarians are free-living flatworms, whose importance in biomedical research lies in their regeneration capacity. Planarians possess a wide population of pluripotent adult stem cells, called neoblasts, which allow them to regenerate any body part after injury. In a recent study, we identified three foxK paralogs in the genome of Schmidtea mediterranea. In this study, we demonstrate that foxK1 inhibition prevents regeneration of the ectodermal tissues, including the nervous system and the epidermis. These results correlate with foxK1 expression in neoblasts and in neural progenitors. Although the triggering of wound genes expression, polarity reestablishment and proliferation was not affected after foxK1 silencing, the apoptotic response was decreased. Altogether, these results suggest that foxK1 would be required for differentiation and maintenance of ectodermal tissues