Localization of planarian β-CATENIN-1 reveals multiple roles during anterior-posterior regeneration and organogenesis

Abstract

The β-catenin-dependent Wnt pathway exerts multiple contextdependent roles in embryonic and adult tissues. In planarians, β-catenin-1 is thought to specify posterior identities through the generation of an anteroposterior gradient. However, the existence of such a gradient has not been directly demonstrated. Here, we use a specific polyclonal antibody to demonstrate that nuclear β-CATENIN-1 exists as an anteroposterior gradient from the pre-pharyngeal region to the tail of the planarian Schmidtea polychroa. High levels in the posterior region steadily decrease towards the pre-pharyngeal region but then increase again in the head region. During regeneration, β-CATENIN-1 is nuclearized in both anterior and posterior blastemas, but the canonical WNT1 ligand only influences posterior nuclearization. Additionally, β-catenin-1 is required for proper anterior morphogenesis, consistent with the high levels of nuclear β-CATENIN-1 observed in this region. We further demonstrate that β-CATENIN-1 is abundant in developing and differentiated organs, and is particularly required for the specification of the germline. Altogether, our findings provide the first direct evidence of an anteroposterior nuclear β-CATENIN-1 gradient in adult planarians and uncover novel, context-dependent roles for β-catenin-1 during anterior regeneration and organogenesis.

Rebuilding a planarian: from early signaling to final shape

“…Answering this question has been the recent focus of several research groups. It is now known that a gradient of b-catenin activity, which is regulated by a morphogenetic gradient of "posterior Wnts", patterns gene expression along the planarian AP axis (Iglesias et al, 2008;Petersen and Reddien, 2008;Gurley et al, 2008;Adell et al, 2010;Sureda-Gómez et al, 2016). The findings of a recent mathematical modeling study suggest that this gradient occurs autonomously in the tail and that it takes part of a self-organizing patterning system that patterns the AP axis during homeostasis and regeneration (Stückemann et al, 2017).…”

“…The hierarquichal relationship between the A and the P pole genes is still not well resolved. bcatenin1 is also expressed in the A pole, where it could activate the expression of its own inhibitor, notum (Petersen and Reddien 2011;Sureda-Gómez et al, 2016). pbx and follistatin are required for the specification of both poles.…”

“…Similarly, more studies are required to characterize the mechanisms by which these transcription factors regulate the terminal differentiation of planarian neurons (i.e., to identify downstream elements and/or determine how transcription factors interact with different signaling pathways). Two recent studies have described the role of the Hedgehog and Wnt/b-catenin pathways in neural cell differentiation (Currie et al, 2016;Sureda-Gómez et al, 2016). Silencing of b-catenin-1 results in the regeneration of smaller brains containing reduced numbers of octopaminergic and dopaminergic neurons (Sureda-Gómez et al, 2016).…”

“…Two recent studies have described the role of the Hedgehog and Wnt/b-catenin pathways in neural cell differentiation (Currie et al, 2016;Sureda-Gómez et al, 2016). Silencing of b-catenin-1 results in the regeneration of smaller brains containing reduced numbers of octopaminergic and dopaminergic neurons (Sureda-Gómez et al, 2016). The transcription factors nkx2.1 and arx are expressed in some ventralmedial (VM) neuronal types, including cholinergic, GABAergic, and octopaminergic neurons, and in Smedwi-1-expressing progenitors.…”

Multi-scale coordination of planar cell polarity in planarians

“…Such anatomical plasticity is rooted in the continuous renewal of all cell types via constantly dividing pluripotent adult stem cells (neoblasts) and the requisite need for patterning signals to mediate location-dependent cell fate choices (Rink, 2012). A Wnt signaling gradient emanating from the tail is a core component of planarian A/P patterning (Reuter et al, 2015;Stückemann et al, 2017;Sureda-Gómez et al, 2016) and experimental interference with Wnt signaling consequently result in the spectacular reprogramming of organismal head/tail polarity. Additionally, the cilia-driven directional gliding motility of planarians provides clear indications of cell-level polarity.…”