title: Novel Tfap2-mediated control of soxE expression facilitated the evolutionary emergence of the neural crest.
abstract: Gene duplication has been proposed to drive the evolution of novel morphologies. After gene duplication, it is unclear whether changes in the resulting paralogs' coding-regions, or in their cis-regulatory elements, contribute most significantly to the assembly of novel gene regulatory networks. The Transcription Factor Activator Protein 2 (Tfap2) was duplicated in the chordate lineage and is essential for development of the neural crest, a tissue that emerged with vertebrates. Using a tfap2-depleted zebrafish background, we test the ability of available gnathostome, agnathan, cephalochordate and insect tfap2 paralogs to drive neural crest development. With the exception of tfap2d (lamprey and zebrafish), all are able to do so. Together with expression analyses, these results indicate that sub-functionalization has occurred among Tfap2 paralogs, but that neo-functionalization of the Tfap2 protein did not drive the emergence of the neural crest. We investigate whether acquisition of novel target genes for Tfap2 might have done so. We show that in neural crest cells Tfap2 directly activates expression of sox10, which encodes a transcription factor essential for neural crest development. The appearance of this regulatory interaction is likely to have coincided with that of the neural crest, because AP2 and SoxE are not co-expressed in amphioxus, and because neural crest enhancers are not detected proximal to amphioxus soxE. We find that sox10 has limited ability to restore the neural crest in Tfap2-deficient embryos. Together, these results show that mutations resulting in novel Tfap2-mediated regulation of sox10 and other targets contributed to the evolution of the neural crest.
authors.affiliation: Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, IA 52242, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Otterloo
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Aaron
authors.initials: A
authors.lastname: Garnett
authors.forename: Maria
authors.initials: M
authors.lastname: Cattell
authors.forename: Daniel Meulemans
authors.initials: DM
authors.lastname: Medeiros
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cornell
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005075:Biological Evolution; D043344:Chordata / Q000033:anatomy & histology / Q000145:classification / Q000196:embryology / Q000235:genetics; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics; D004627:Embryonic Induction; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007798:Lampreys / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics; D009432:Neural Crest / Q000166:cytology / Q000502:physiology*; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics
chemical_list: D051698:Activating Transcription Factor 2; D020033:Protein Isoforms; D055757:SOXE Transcription Factors