Whole-Body Acoel Regeneration Is Controlled by Wnt and Bmp-Admp Signaling

Abstract

Whole-body regeneration is widespread in the Metazoa, yet little is known about how underlying molecular mechanisms compare across phyla. Acoels are an enigmatic phylum of invertebrate worms that can be highly informative about many questions in bilaterian evolution, including regeneration. We developed the three-banded panther worm, Hofstenia miamia, as a new acoelomorph model system for molecular studies of regeneration. Hofstenia were readily cultured, with accessible embryos, juveniles, and adults for experimentation. We developed molecular resources and tools for Hofstenia, including a transcriptome and robust systemic RNAi. We report the identification of molecular mechanisms that promote whole-body regeneration in Hofstenia. Wnt signaling controls regeneration of the anterior-posterior axis, and Bmp-Admp signaling controls regeneration of the dorsal-ventral axis. Perturbation of these pathways resulted in regeneration-abnormal phenotypes involving axial feature duplication, such as the regeneration of two heads following Wnt perturbation or the regeneration of ventral cells in place of dorsal ones following bmp or admp RNAi. Hofstenia regenerative mechanisms are strikingly similar to those guiding regeneration in planarians. However, phylogenetic analyses using the Hofstenia transcriptome support an early branching position for acoels among bilaterians, with the last common ancestor of acoels and planarians being the ancestor of the Bilateria. Therefore, these findings identify similar whole-body regeneration mechanisms in animals separated by more than 550 million years of evolution.

Xenacoelomorpha: a case of independent nervous system centralization?

“…This is an intriguing issue, for it has been observed that acoels do not have, apparently, an obvious preference for ventral or dorsal NS localization. However, in a preliminary study, and in the context of animal regeneration, it has been shown that the acoel Hofstenia miamia have differential expression of BMPs (bone morphogenetic proteins) and their antagonistic ADMPs (anti-dorsalizing morphogenetic proteins) along this secondary axis [72]. How the expression of these genes is related to the position of the neurite bundles can be, at present, just a matter of speculation.…”

“…Previous studies carried out by Srivastava et al [72] in H. miamia found five Wnt homologues which were branching together with one Wnt relative of the cnidarian Hydra vulgaris. We decided to try including those Wnt protein sequences in our analysis and see how they were placed in relationship to the Wnt relatives in our acoel species.…”

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

“…Thus, β-catenin acts as a master regulatory gene, responsible for the control of multiple processes. During early animal embryogenesis, β-catenin specifies the site of endoderm internalization and promotes posterior fates in most studied systems (Byrum and Wikramanayake, 2013;Darras et al, 2011;Haegel et al, 1995;Henry et al, 2008;Lee et al, 2006;Logan et al, 1999;Srivastava et al, 2014;Wikramanayake et al, 2003). In later stages of development, the canonical Wnt pathway influences the formation of multiple cell types, tissues and organ systems (Aulehla et al, 2008;Grigoryan et al, 2008;Hari et al, 2002;Holland et al, 2005;Kiecker and Niehrs, 2001; Lewis et al, 2004;Petersen and Reddien, 2009a;Schneider and Bowerman, 2007;Tan et al, 2006;Watanabe et al, 2014), and most prominently, the anteroposterior (AP) patterning of the vertebrate central nervous system (Ciani and Salinas, 2005).…”

Acoelomorpha: earliest branching bilaterians or deuterostomes?

“…All the ML and Bayerian analyses, which used GTR or WAG models, displayed Acoelomorpha as the sister group to the rest of Bilateria, while the Bayesian tress generated using CAT or CAT+GTR models recovered paraphyletic deuterostomes and acoelomorphs as sister to protostomes (Table 1). Importantly, none of the analyses of Ryan et al (2013) or Srivastava et al (2014) showed Acoelomorpha as sister group or within Deuterostomia.…”

“…Finally, Srivastava et al (2014) published a study on the regeneration mechanisms of acoels which included extensive phylogenomic analyses focused on resolving the position of Acoelomorpha and Xenoturbella. All the ML and Bayerian analyses, which used GTR or WAG models, displayed Acoelomorpha as the sister group to the rest of Bilateria, while the Bayesian tress generated using CAT or CAT+GTR models recovered paraphyletic deuterostomes and acoelomorphs as sister to protostomes (Table 1).…”