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

Marta Truchado-García, Kimberly J. Perry, Florencia Cavodeassi, Nathan J. Kenny, Jonathan Q. Henry, Cristina Grande

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbermsac270
JournalMolecular biology and evolution
Issue number2
StatePublished - Feb 1 2023


  • Crepidula fornicata
  • EvoDevo
  • Nodal
  • Spiralia
  • cripto
  • gene expression pattern
  • left-right asymmetry
  • zebrafish

ASJC Scopus subject areas

  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology


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