Landmarks in Existing Tissue at Wounds Are Utilized to Generate Pattern in Regenerating Tissue

Abstract

Summary Regeneration in many organisms involves the formation of a blastema, which differentiates and organizes into the appropriate missing tissues. How blastema pattern is generated and integrated with pre-existing tissues is a central question in the field of regeneration. Planarians are free-living flatworms capable of rapidly regenerating from small body fragments [1]. A cell cluster at the anterior tip of planarian head blastemas (the anterior pole) is required for establishment of anterior-posterior (AP) and midline blastema pattern [2–4]. Transplantation of the head tip into tails induced host tissues to grow patterned head-like outgrowths containing a midline. Given the important patterning role of the anterior pole, understanding how it becomes localized during regeneration would help explain how wounds establish pattern in new tissue. Anterior pole progenitors were specified at the pre-existing midline of regenerating fragments, even when this location deviated from the medial-lateral (ML) median plane of the wound face. Anterior pole progenitors were specified broadly on the dorsal-ventral (DV) axis, and subsequently formed a cluster at the DV boundary of the animal. We propose that three landmarks of pre-existing tissue at wounds set the location of anterior pole formation – a polarized AP axis, the pre-existing midline, and the dorsal-ventral median plane. Subsequently, blastema pattern is organized around the anterior pole. This process, utilizing positional information in existing tissue at unpredictably shaped wounds, can influence patterning of new tissue in a manner that facilitates integration with pre-existing tissue in regeneration.

foxF-1 Controls Specification of Non-body Wall Muscle and Phagocytic Cells in Planarians

“…nk4 and gata4/5/6–2 RNAi head blastemas were cyclopic and had perturbed expression domains of midline genes (Figure 4B; Figure S6A,B). This ML-patterning phenotype was similar to that of regenerating animals lacking the anterior pole, a group of notum-expressing cells that function as an organizer of the anterior and midline blastema regions [26, 27]. However, anterior-pole cells were still present in these RNAi animals (Figure 4B).…”

Self-organization and progenitor targeting generate stable patterns in planarian regeneration

“…The slit medial expression domain is restricted by laterally expressed wnt5 (29). wnt5 and slit RNAi can impact ML eye formation (30). Following wnt5 RNAi, serial eye nucleation was observed, progressing laterally as slit expression boundaries expanded (Fig.…”

Multi-scale coordination of planar cell polarity in planarians

“…This observation is interesting because the same regions are also implicated in the specification of the cardinal body axes of the planarian body plan. Signals expressed by the margin cells participate in midline and D/V patterning (Adell et al, 2009;Gaviño and Reddien, 2011;Gurley et al, 2010), while a small group of cells at the head and tail tips are thought to function as "organizers" of the planarian head and tail (Blassberg et al, 2013;Chen et al, 2013;Oderberg et al, 2017;Vásquez-Doorman and Petersen, 2014;Vogg et al, 2014). These so-called pole cells regenerate in a pbx-dependent manner and the headless and tailless animals resulting from pbx(RNAi) are one of the lines of evidence that support the critical patterning role of these cells (Blassberg et al, 2013;Chen et al, 2013).…”

“…3G) (Blassberg et al, 2013;Chen et al, 2013). pbx(RNAi) prevents formation of the head and tail poles that are thought to act as organizers of the planarian A/P axis (Oderberg et al, 2017;Reuter et al, 2015;Vásquez-Doorman and Petersen, 2014;Vogg et al, 2014). Remarkably, pbx(RNAi) animals still displayed coherent long-range polarity ( Fig.…”

“…4C). The latter necessitates restriction of the head boundary effect (H) to the head tip, which corresponds to the presumed location of the planarian head organizer (Chen et al, 2013;Oderberg et al, 2017;Vásquez-Doorman and Petersen, 2014;Vogg et al, 2014) and thus has important implications regarding the alignment of polarity vectors with the cardinal body axes (see discussion). Further, recapitulation of the A/P gradation of the splay pattern despite the presumed globally uniform radial polarization effect of the body margin requires the tail to be more strongly polarizing than the head ( + /b + > -/b -), which then results in the graded relative contribution of the M """⃗ field along the A/P axis.…”