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Positional information in planarian muscle

In my las post before the summer break I commented on three papers that had reported how the silencing of a single gene, B-catenin1, was able to rescue head regeneration in three different species of planarians that usually do not regenerate their heads, when amputated post-pharyngeally. Now, in this first post after the holidays I go back to planarians to comment on the recent findings by the laboratory of Peter Reddien on positional information (http://www.ncbi.nlm.nih.gov/pubmed/23954785). As the authors state in their paper, during regeneration, in addition to new cells required for rebuilding the missing structures, these cells must obey very strict instructions in order to be able to form the proper tissues and organs in the appropriate territories. In this sense, no much is known about how positional identities are maintained and re-established during planarian regeneration. Previous studies from the laboratory of Kiyokazu Agata had suggested that such positional information resided in differentiated cells (http://www.ncbi.nlm.nih.gov/pubmed/11319861). Now, the new data from the Reddien’s lab points out that are the muscle cells that would provide such instructions during regeneration.

 First, the authors define the position control genes (PCGs), as genes that (i) display regionalized expression along one or more body axes, and (ii) either their RNAI-mediated silencing results in a patterning defect or encode a protein related to the Wnt, BMP or FGF signalling pathways that are involved in is patterning. These PCGs include: notum, sfrp-1,sfrp-2, several wnts, fz-4, prep, ndk, ndl-3, ndl-4, netrin-2, bmp, admp, ngl-7, ngl-8, nog-1, nog-2 and tolloid. The expression patterns and functions of these genes have been reported in recent years. Interestingly, all these PCGs are expressed in a population of uncharacterized subepidermal differentiated cells. So, the authors wondered whether those cells could represent the source of positional information in planarians.

By doing in situ hybridization with multiple combinations of all the PCGs they found first that many of them co-localized in those subepidermal cells. Next, they found that subepidermal muscle cells that co-expressed collagen, troponin and tropomyosin displayed a similar distribution of those expressing PCGs. Remarkably, every PCG tested was co-expressed with collagen or troponin, suggesting that muscle cells may provide instructive signalling during planarian regeneration. Quantitatively, between 95,7% and 99,8% of all muscle cells analyzed from different body regions co-express PCGs. Although most PCGs are expressed in the subepidermal body wall musculature, others are also expressed in the muscle cells that surround the digestive system or the pharyngeal muscle.

 Finally, the authors analyzed whether the expression of these PCGs was regulated in muscle cells after amputation. Thus, for example, the polarity determinants notum and wnt1 are rapidly induced after amputation in muscle cells. Importantly, this expression occurs in irradiated (neoblast-depleted) animals, suggesting that the existing muscle cells are able to dynamically change the expression of PCGs in them as response to amputation. Moreover, muscle cells are able to re-adjust the profile of the PCGs that express to the one corresponding to the new region along the body axes in which they are placed after amputation.

 Overall the authors propose a model in which changes in the expression of PCGs in muscle cells at the wound regions would influence neoblast cell fate according to their new positions. In the future it would be interesting to test this model by trying to analyze the regenerative capabilities of muscle-deficient planarians (if that is really possible). 

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2 Comments

  1. Jaume Baguñà says:

    This is a very important paper because for the first time it shows that positional information in planarians (AP, DV, right-left) seems to reside in differentiated cells; more particular, in muscle cells. And I consider it important because it shows that irrespective of the presence of neoblasts, expression of positional markers change during wound closure and regeneration in doomed neoblast-free animals. Therefore, neoblasts should, somehow, be instructed by differentiated cells to turn into different sorts of differentiated cells according to their axial position. Some hints that differentiated cells and not neoblasts were the bearers of positional information came, as the authors acknowledge, from an almost 30 years old, underquoted paper, by Saló and Baguñà (1985) on intercalary regeneration published in Roux’s Archives Dev Biol (now Genes, Develop. Evol).

    As could not be otherwise, the paper raises a lot of interesting and pressing questions. Let’s assume that muscle cells bear positional information in form of presence/absence and/or different levels of positional control genes (PGCs) and that its expression changes during regeneration. Question is: which ‘signal’ instructs muscle cells to activate/inhibit or change the PGCs expression levels in muscle cells during regeneration? In other words, it makes sense to think that ‘something’ MUST BE activated/inhibited during regeneration instructing muscle cells to activate/inhibit/change PGCs’ expression which, in turn, will instruct neoblasts nearby to set to specific cell lineages to give rise to what is needed. Any hint on the nature of that signal? Honestly no idea, though nerve tracts products (may be through GJ), and/or epithelial-mesenchymal interactions should be looked carefully.

    A second set of questions is whether, besides axial positional information, cells other than muscle cells also bear positional information as regards more internal tissues, outside/inside polarity, or merely tissue or cell type information. The answer should be yes. Neoblasts are everywhere and they should be ‘instructed’ by local signals released by local differentiated cells to proliferate or to shift to different cell types.

    And the final, main, question. How is the set of different positional information systems, axial or not, regulated whole? Is there a master system/tissue? Or does morphology results merely from different positional systems working in parallel giving rise to organisms with selectively fit phenotypes?

    By the way. My sincere congratulations to the Reddien lab for going/looking at the cell level and for producing for the first time in situs on isolated CELLS, skipping for a while the boring Whole Mounts. For almost 20 years I prompted many people to do it, to no avail. Now that’s it.

    MANY, MANY THANKS.

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    • The idea that muscle fibers can provide positional information during planarian regeneration is intriguing and, definitively, will deserve further analyses and confirmation. In this sense it would be interesting to check for example what happens if the differentiation of new muscle fibers is inhibited during regeneration. These results made me think about some old experiments I did during my PhD. There, we saw that the dynamics of body-wall muscle restoration during anterior regeneration appeared different between dorsal and ventral surfaces (Cebrià and Romero, 2001, Belgian Journal of Zoology 131 suppl: 111-115). Thus, ventrally, the blastemas appeared to contain always preexisting muscle fibers, specially longitudinal ones. In contrast, the wound appeared shifted dorsally and during the first days appeared (from the dordal side) devoid of muscle fibers that start differentiating after 2-3 days. At that time we thought that these differences could be related to the way that the wound was healed during anterior regeneration. Old studies by Chandebois had suggested that the wound is differentially healed during anterior or posterior regeneration. She suggested that during anterior regeneration is the dorsal epithelium that stretches to heal the wound; on the other side, the ventral epithelium would heal the wound during posterior regeneration. This difference could be relevant for the re-establishment of the AP polarity. However, since Chandebois and up to my knowledge, there are no recent published studies revisiting this hypothesis with molecular markers. Going back to the musculature, a paper by Willi Salvenmoser and Peter Ladurner (2001, Belgian Journal of Zoology 131 suppl: 105-109) showed that in the flatworm Macrostomum sp. during posterior regeneration, the dorsal shift of the wound that we saw in Schmidtea mediterranea, appeared ventrally. That is during posterior regeneration in Macrostomum sp., the dorsal blastema contains always preexisting muscles while ventrally the wound appears devoid of muscles during the early stages of regeneration. At that time we did not checked the dynamics of muscle pattern restoration during posterior regeneration in S. mediterranea but after this paper by the laboratory of Peter Reddien maybe it would be worthy to analyze whether preexisting and novel muscle fibers behave differently in anterior and posterior blastemas and if those differences could have a role on polarity or identity.

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Francesc Cebrià

Francesc Cebrià

Francesc Cebrià

I am a Biologist and Professor at the University of Barcelona. I do my research on a fascinating animal: freshwater planarians. You can cut them in as many pieces as you want and each piece will regenerate a complete new flatworm in very few days. In this blog I will keep you updated on the latest news on the field of animal regeneration. You will be able to follow the latest research on how planarians, axolotls, newts, cnidarians and other animals are able to regenerate parts of their bodies

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