A Small Change With a Twist Ending: A Single Residue in EGF-CFC Drives Bilaterian Asymmetry. (20th December 2022)

• Record Type: Journal Article
• Authors: Truchado-García, Marta; Perry, Kimberly J; Cavodeassi, Florencia; Kenny, Nathan J; Henry, Jonathan Q; Grande, Cristina
• Editors: Parsch, John
• Is Part Of: Molecular biology and evolution. Volume 40:Number 2(2023)
• Publication Date: 2022-12-20
• Subjects: Nodal -- EGF-CFC -- cripto -- left-right asymmetry -- zebrafish -- EvoDevo -- gene expression pattern -- Spiralia -- Crepidula fornicata; Molecular biology -- Periodicals; Molecular evolution -- Periodicals; Evolution, Molecular -- Periodicals; Molecular Biology -- Periodicals; 572.8
• DOI: 10.1093/molbev/msac270
• Languages: English
• ISSNs: 0737-4038

Abstract

Abstract: Asymmetries are essential for proper organization and function of organ systems. Genetic studies in bilaterians have shown signaling through the Nodal/Smad2 pathway plays a key, conserved role in the establishment of body asymmetries. Although the main molecular players in the network for the establishment of left-right asymmetry (LRA) have been deeply described in deuterostomes, little is known about the regulation of Nodal signaling in spiralians. Here, we identified orthologs of the egf-cfc gene, a master regulator of the Nodal pathway in vertebrates, in several invertebrate species, which includes the first evidence of its presence in non-deuterostomes. Our functional experiments indicate that despite being present, egf-cfc does not play a role in the establishment of LRA in gastropods. However, experiments in zebrafish suggest that a single amino acid mutation in the egf-cfc gene in at least the common ancestor of chordates was the necessary step to induce a gain of function in LRA regulation. This study shows that the egf-cfc gene likely appeared in the ancestors of deuterostomes and "protostomes", before being adopted as a mechanism to regulate the Nodal pathway and the establishment of LRA in some lineages of deuterostomes.