WNT-FRIZZLED-LRP5/6 Signaling Mediates Posterior Fate and Proliferation during Planarian Regeneration

Abstract

An organizer is defined as a group of cells that secrete extracellular proteins that specify the fate of surrounding cells according to their concentration. Their function during embryogenesis is key in patterning new growing tissues. Although organizers should also participate in adult development when new structures are regenerated, their presence in adults has only been identified in a few species with striking regenerative abilities, such as planarians. Planarians provide a unique model to understand the function of adult organizers, since the presence of adult pluripotent stem cells provides them with the ability to regenerate any body part. Previous studies have shown that the differential activation of the WNT/β-catenin signal in each wound is fundamental to establish an anterior or a posterior organizer in the corresponding wound. Here, we identify the receptors that mediate the WNT/β-catenin signal in posterior-facing wounds. We found that Wnt1-Fzd1-LRP5/6 signaling is evolutionarily conserved in executing a WNT/β-catenin signal to specify cell fate and to trigger a proliferative response. Our data allow a better understanding of the mechanism through which organizers signal to a “competent” field of cells and integrate the patterning and growth required during de novo formation of organs and tissues.

Extensive loss of Wnt genes in Tardigrada

“…The specific orthology of this sequence is unclear based on our analyses. The S. mediterranea sequence represents a highly derived Arrow/LRP5/6 ortholog based on functional analyses [ 98 ] …”

“…S. mediterranea encoded a gene that was a reciprocal best BLAST hit to D. melanogaster Arrow (Additional file 2 : S1). This gene had been identified as an ortholog of arrow / Lrp5/6 in a previous study [ 98 ]. The best BLAST hits from the remaining species did not encode the pattern of protein domains that is typical of Arrow (Fig.…”

“…Lower case letters after taxon names indicate unclear orthology. The orthology of the S. mediterranea LRP5/6 sequence is based on functional analyses [ 98 ]. Species abbreviations: Ad, Adineta vaga ; Ce, Caenorhabditis elegans ; Dg, Dimorphilus gyrociliatus ; Dm, Drosophila melanogaster ; Ek, Euperipatoides kanangrensis ; He, Hypsibius exemplaris ; Hm, Hofstenia miamia ; Mm, Mus musculus ; Ob, Octopus bimaculoides ; Rv, Ramazzottius varieornatus ; Sm, Schmidtea mediterranea ; Tc, Tribolium castaneum …”

“…Evidence for an additional role of arrow / Lrp5/6 comes from studies of the flatworm S. mediterranea . In this species, this gene is required to regulate posterior cell fate and proliferation during AP axis regeneration [ 98 ]. Second, given the sparse data available in regards to which Wnt gene regulates posterior growth, and the apparent interchangeability of Wnt gene function in this process based on data that are available [ 26 , 58 ], it is not possible to associate with confidence the loss of any particular Wnt gene in tardigrades with the loss of posterior growth.…”

The Evolution of Invertebrate Animals

“…This volume is clearly not intended to be an exhaustive collection of studies on invertebrate animals, but we hope that the collection of articles presented here will give a general idea of both the type of studies carried out with invertebrate metazoans and the diversity of animal models used. Thus, we can read works carried out with Acropora corals [ 1 ], with several mollusc species such as the cephalopod Nautilus pompilius [ 2 ], the gastropod Crepidula fornicata [ 3 ] or the bivalve Mytilus galloprovincialis [ 4 ], as well as a study with the planarian Schmidtea mediterranea [ 5 ], or with several chordates such as two cephalochordate species ( Branchiostoma lanceolatum [ 6 ] and Branchiostoma floridae [ 7 ]) and two urochordate species ( Ciona robusta [ 8 ] and Phallusia mammillata [ 4 ]).…”