Nematostella vectensis, an Emerging Model for Deciphering the Molecular and Cellular Mechanisms Underlying Whole-Body Regeneration

Abstract

The capacity to regenerate lost or injured body parts is a widespread feature within metazoans and has intrigued scientists for centuries. One of the most extreme types of regeneration is the so-called whole body regenerative capacity, which enables regeneration of fully functional organisms from isolated body parts. While not exclusive to this habitat, whole body regeneration is widespread in aquatic/marine invertebrates. Over the past decade, new whole-body research models have emerged that complement the historical models Hydra and planarians. Among these, the sea anemone Nematostella vectensis has attracted increasing interest in regard to deciphering the cellular and molecular mechanisms underlying the whole-body regeneration process. This manuscript will present an overview of the biological features of this anthozoan cnidarian as well as the available tools and resources that have been developed by the scientific community studying Nematostella. I will further review our current understanding of the cellular and molecular mechanisms underlying whole-body regeneration in this marine organism, with emphasis on how comparing embryonic development and regeneration in the same organism provides insight into regeneration specific elements.

Keywords: Nematostella vectensis; anthozoa; cnidaria; functional genomics; marine organism; regeneration; sea anemone; stress response; whole-body regeneration.

Figure 1

(A) Simplified metazoan phylogeny, emphasizing the position of cnidaria as a sister group to bilaterians as well as the cnidarian phylogeny highlighting the relationships between the major groups. CBA (cnidarian-bilaterian ancestor). Data based on [89,90]. (B) Adult Nematostella polyp. (*) mouth, (ten) tentacles, (pha) pharynx, (mes) mesenteries (phy) physa. Figure modified from [91,92]. (C) Schematic cross section of a complete/adult mesenteries at the gonadal section (adapted from [83,93]). (p-ecto) pharyngeal ectoderm, (ecto) ectoderm, (rM) retractor muscle, (pM) parietal muscle, (cM) circular muscle.

Figure 2

Schematic representation of the various developmental trajectories and the phenotypic plasticity of Nematostella: Embryonic development, polarity reversal, physal pinching, degrowth and regrowth, whole-body regeneration (modified from [92]).

Figure 3

Overview of the morphological hallmarks characterizing whole-body regeneration in Nematostella. Confocal images of DAPI (nuclei in cyan) stained regenerating oral regions of juvenile Nematostella polyps (a–e) represent the characteristic phenotype of a given regeneration step. The panel spans 144 hours of regeneration and indicates the proliferation independent (steps 0, 1) and dependent (steps 2–4) steps of the process. The arrows below indicate the beginning of measurable tissular, cellular, and molecular events. The red dashed line indicates the amputation plane and the yellow arrow heads highlight tentacle buds/elongating tentacles; (m) mesenteries, (pha lip) pharyngeal lip, (pha) pharynx, (*) mouth opening (modified from [21,77,99]).

Figure 4

Current model of the cellular dynamics underlying whole body regeneration in Nematostella. Following sub-pharyngeal amputation, the tissue crosstalk between the mesenteries and the body wall epithelia at the amputation site triggers a regenerative response via the activation of two potential stem cell population (yellow and blue) that migrate towards the amputation site where they start dividing and participate in the reformation of lost body parts (modified from [21,77,99].

Figure 5

Regeneration is a modest transcriptomic event compared to embryonic development. Comparison of the transcriptomic time series during embryonic development and regeneration revealed that regeneration is reactivating a modest number of genes transcriptionally dynamic during embryonic development. Interestingly, this comparative approach also enables the identification of genes with a regeneration-specific expression dynamics (adapted from [21,35,56]).