Characterization of bilaterian head patterning genes in a cnidarian reveals a key role for six3/6 in aboral domain development and provides new insight into the evolutionary origin of head development.
The origin of the bilaterian head is a fundamental question for the evolution of animal body plans. The head of bilaterians develops at the anterior end of their primary body axis and is the site where the brain is located. Cnidarians, the sister group to bilaterians, lack brain-like structures and it is not clear whether the oral, the aboral, or none of the ends of the cnidarian primary body axis corresponds to the anterior domain of bilaterians. In order to understand the evolutionary origin of head development, we analysed the function of conserved genetic regulators of bilaterian anterior development in the sea anemone Nematostella vectensis. We show that orthologs of the bilaterian anterior developmental genes six3/6, foxQ2, and irx have dynamic expression patterns in the aboral region of Nematostella. Functional analyses reveal that NvSix3/6 acts upstream of NvFoxQ2a as a key regulator of the development of a broad aboral territory in Nematostella. NvSix3/6 initiates an autoregulatory feedback loop involving positive and negative regulators of FGF signalling, which subsequently results in the downregulation of NvSix3/6 and NvFoxQ2a in a small domain at the aboral pole, from which the apical organ develops. We show that signalling by NvFGFa1 is specifically required for the development of the apical organ, whereas NvSix3/6 has an earlier and broader function in the specification of the aboral territory. Our functional and gene expression data suggest that the head-forming region of bilaterians is derived from the aboral domain of the cnidarian-bilaterian ancestor.
The evolutionary origin of head development is a fundamental question for understanding the evolution of animal body plans. Bilaterally symmetrical animals (Bilaterians) have an anterior-posterior (head-to-tail) axis, whose anterior end is usually characterized by a nervous system centralization, the brain. This region is often associated with a distinct structure, the head, and its development is regulated by a set of conserved transcription factors and signalling molecules. Bilaterians evolved from an ancestor shared with cnidarians (corals, sea anemones, jellyfish), but brain-like structures are absent in cnidarians, although they have an obvious oral-aboral axis. Cnidarian larvae move with the aboral pole forward, but as adult polyps this pole is anchored to the ground, while the oral end is used for feeding. It is unclear whether one of the termini of cnidarians corresponds to the bilaterian head-forming region. We show here that in the sea anemone Nematostella vectensis genes regulating bilaterian head development are expressed at the larval aboral pole and that a key anterior developmental gene, six3/6, controls the development of the aboral pole. These findings support the hypothesis that the anterior, head-forming, region of bilaterians and the aboral region of cnidarians derived from the same domain of their last common ancestor and are therefore homologues.