4.8 Article

A Small Change With a Twist Ending: A Single Residue in EGF-CFC Drives Bilaterian Asymmetry

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MOLECULAR BIOLOGY AND EVOLUTION
卷 40, 期 2, 页码 -

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OXFORD UNIV PRESS
DOI: 10.1093/molbev/msac270

关键词

Nodal; EGF-CFC; cripto; left-right asymmetry; zebrafish; EvoDevo; gene expression pattern; Spiralia; Crepidula fornicata

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Asymmetries are crucial for the proper organization and function of organ systems. The Nodal/Smad2 pathway has been shown to play a key role in the establishment of body asymmetries in bilaterians. In this study, the orthologs of the egf-cfc gene, a master regulator of the Nodal pathway, were identified in invertebrate species, providing evidence of its presence in non-deuterostomes. The functional experiments revealed that egf-cfc does not contribute to the establishment of left-right asymmetry in gastropods, but a mutation in this gene in the common ancestor of chordates was found to induce a gain of function in LRA regulation.
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.

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