Linking Vertebrate Gene Duplications to the New Head Hypothesis

SIMPLE SUMMARY: Neural crest cells are unique to vertebrates and migrate long distances throughout the embryo and give rise to many cell and tissue types, including bone, cartilage, smooth muscle, and peripheral nerves. Neural crest cells express many genes that are also expressed in the neural plate border, cartilage, and neurons of invertebrate chordates. However, in neural crest cells, these genes interact as a novel gene regulatory network unique to vertebrates. Much of the vertebrate head is built from neural crest cells, and the evolutionary flexibility of the vertebrate head is thought to have facilitated the evolution of new vertebrate groups. The genomes of vertebrates also show evidence of repeated genome duplication events. However, it is not clear whether these duplications were necessary for the evolution of neural crest cells and thus the vertebrate head. Here, we discuss the general architecture of the gene regulatory network driving neural crest development and highlight gene families within the network that have diverged following duplication events. Based on these analyses, we conclude that the origin of neural crest cells and the neural crest gene regulatory network were not dependent on the vertebrate genome duplications. However, these duplications may have facilitated the diversification of neural crest derivatives, including the head skeleton. ABSTRACT: Vertebrates have diverse morphologies and various anatomical novelties that set them apart from their closest invertebrate relatives. A conspicuous head housing a large brain, paired sense organs, and protected by a skeleton of cartilage and bone is unique to vertebrates and is a defining feature of this taxon. Gans and Northcutt (1980s) proposed that the evolution of this “new head” was dependent on two key developmental innovations: neural crest cells (NCCs) and ectodermal placodes. NCCs are migratory embryonic cells that form bone, cartilage, and neurons in the new head. Based on genome size, Ohno (1970s) proposed a separate hypothesis, stating that vertebrate genome content was quadrupled via two rounds (2R) of whole genome duplications (WGDs), and the surplus of genetic material potentiated vertebrate morphological diversification. While both hypotheses offer explanations for vertebrate success, it is unclear if, and how, the “new head” and “2R” hypotheses are linked. Here, we consider both hypotheses and evaluate the experimental evidence connecting the two. Overall, evidence suggests that while the origin of the NC GRN predates the vertebrate WGDs, these genomic events may have potentiated the evolution of distinct genetic subnetworks in different neural crest subpopulations. We describe the general composition of the NC GRN and posit that its increased developmental modularity facilitated the independent evolution of NC derivatives and the diversification of the vertebrate head skeleton. Lastly, we discuss experimental strategies needed to test whether gene duplications drove the diversification of neural crest derivatives and the “new head”.