Posterior Wnts Have Distinct Roles in Specification and Patterning of the Planarian Posterior Region

Abstract

The wnt signaling pathway is an intercellular communication mechanism essential in cell-fate specification, tissue patterning and regional-identity specification. A βcatenin-dependent signal specifies the AP (Anteroposterior) axis of planarians, both during regeneration of new tissues and during normal homeostasis. Accordingly, four wnts (posterior wnts) are expressed in a nested manner in central and posterior regions of planarians. We have analyzed the specific role of each posterior wnt and the possible cooperation between them in specifying and patterning planarian central and posterior regions. We show that each posterior wnt exerts a distinct role during re-specification and maintenance of the central and posterior planarian regions, and that the integration of the different wnt signals (βcatenin dependent and independent) underlies the patterning of the AP axis from the central region to the tip of the tail. Based on these findings and data from the literature, we propose a model for patterning the planarian AP axis.

Two FGFRL-Wnt circuits organize the planarian anteroposterior axis

“…In the case of regeneration, animals initially regenerated a single mouth/pharynx, but as regenerating animals grew following feeding, ectopic mouths and pharynges emerged. Inhibition of the posterior mRG wntP-2/wnt11-5 also caused ectopic mouth and pharynx formation ( Figure 3A–C , Figure 3—figure supplement 1A–D ), in agreement with a recent report ( Sureda-Gómez et al, 2015 ). Double RNAi of ndl-3 and wntP-2 was synergistic ( Figure 3A , Fisher’s exact test p<0.0001 for ndl-3, p=0.0153 for wntP-2 , Figure 3—figure supplement 1C ).…”

Antagonistic Self-Organizing Patterning Systems Control Maintenance and Regeneration of the Anteroposterior Axis in Planarians

“…The A/P gradation of the Wnt signaling profile therefore demonstrates that planarian cells experience different Wnt signaling levels along the A/P axis, much like cells in early vertebrate embryos (Kiecker and Niehrs, 2001). Still, individual cell types may experience Wnt signaling levels different from the local average (e.g., in the brain) and individual Wnts may have specific cellular targets, consistent with recent reports of tail Wnt-specific RNAi phenotypes (Lander and Petersen, 2016;Scimone et al, 2016;Sureda-Gó mez et al, 2015). However, our findings indicate that the abundant pluripotent planarian stem cells experience position-dependent levels of Wnt signaling and, consequently, position-specific expression of Wnt target genes.…”

Rebuilding a planarian: from early signaling to final shape

“…They demonstrate that ndl-3 (a second FGF-like receptor), expressed in the prepharyngeal region, is required to restrict trunk identity, since its inhibition generates ectopic pharynges and mouths. The same phenotype is observed after inhibition of wnt11-2 (also called wntP-2 or wnt4-b) (Sureda-Gómez et al, 2015). Although the signals that specify the A signaling center need further clarification, together these findings suggest that in planarians the Wnt and FGF pathways coordinate positional identity along the planarian body axis.…”

“…These centers may therefore be essential for proper tissue growth, in addition to providing patterning cues. In support of this view, silencing of pbx, as well as other elements involved in the formation of the A or P planarian poles, results in a no-tail or no-head phenotype instead of a head-to-tail or a tail-to-head transformation, illustrating the requirement of the poles for tissue growth (Petersen and Reddien, 2009;Rink et al, 2009;Petersen and Reddien, 2011;Sureda-Gómez et al, 2015;Adell et al, 2009;Hayashi et al, 2011;Vasquez-Doorman and Petersen, 2014;Scimone et al, 2014;Vogg et al, 2014).…”

“…This finding is of particular significance, given that in other organisms the main role of notum is to inhibit Wnt function. Interestingly, the expression of both secreted elements, notum and wnt1, begins as early as 6 hours post-amputation as a dotted pattern in muscle cells of any wound, and is not restricted to their ultimate location at the A and P poles, respectively, until 24 to 48 hours later (Petersen and Reddien, 2009;Petersen and Reddien, 2011;Sureda-Gómez et al, 2015). This dotted early expression pattern of both genes appears to be independent of proliferation, whereas their expression at the poles requires the proliferation of neoblasts.…”