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).