Smed-Evi/Wntless is required for β-catenin-dependent and-independent processes during planarian regeneration

Teresa Adell,Kerstin Bartscherer,Emili Salò,Michael Boutros

doi:10.1242/dev.033761

Abstract

Planarians can regenerate a whole animal from only a small piece of their body, and have become an important model for stem cell biology. To identify regenerative processes dependent on Wnt growth factors in the planarian Schmidtea mediterranea (Smed), we analyzed RNAi phenotypes of Evi, a transmembrane protein specifically required for the secretion of Wnt ligands. We show that, during regeneration, Smed-evi loss-of-function prevents posterior identity, leading to two-headed planarians that resemble Smed-beta-catenin1 RNAi animals. In addition, we observe regeneration defects of the nervous system that are not found after Smed-beta-catenin1 RNAi. By systematic knockdown of all putative Smed Wnts in regenerating planarians, we identify Smed-WntP-1 and Smed-Wnt11-2 as the putative posterior organizers, and demonstrate that Smed-Wnt5 is a regulator of neuronal organization and growth. Thus, our study provides evidence that planarian Wnts are major regulators of regeneration, and that they signal through beta-catenin-dependent and -independent pathways.

Highlights

Planarians have a nearly unlimited capability of renewing lost body structures
Schmidtea mediterranea (Smed)-evi mRNA mainly localized to the nervous system, the brain/cephalic ganglia (CG) and the ventral nerve cords (VNCs), as well as to the pharynx, and to the mouth
Smed-evi was expressed in the regenerating nervous system and upregulated in the pharynx primordia, as well as in the tips of posterior wounds, suggesting that Smed-evi might be especially important for posterior regeneration

Summary

Introduction

Planarians have a nearly unlimited capability of renewing lost body structures (reviewed by Saló, 2006). Canonical Wnt signaling is transduced through β-catenin, and mediates developmental processes, including axis specification (reviewed by Grigoryan et al, 2008). Some Wnts, such as mammalian Wnt (Slusarski et al, 1997), can signal through β-catenin-independent mechanisms, and control processes, such as cell polarity and directional movement (Witze et al, 2008). Smed-βcatenin silencing leads to a loss of posterior identity and complete anteriorization (‘radial-like hypercephalyzed’ planarians) (Iglesias et al, 2008). These studies suggest that Wnt proteins might be essential organizers of regeneration in planarians, direct evidence is missing

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