Decrypting the phylogenetics history of EGF-CFC proteins Cripto and Cryptic

Abstract

ABSTRACTEGF-CFC proteins are obligate coreceptors for Nodal signaling and are thus required for gastrulation and left-right patterning. Species with multiple family members show evidence of specialization. For example, mouseCriptois required for gastrulation, whereasCrypticis involved in left-right patterning. However, the members of the family across model organisms have little sequence conservation beyond the EGF-CFC domain, posing challenges for determining their evolutionary history and functional conservation. In this study we outline the evolutionary history of the EGF-CFC family of proteins. We traced theEGF-CFCgene family from a single gene in the deuterostome ancestor through its expansion and functional specialization in tetrapods, and subsequent gene loss and translocation in eutherian mammals. MouseCriptoandCryptic, zebrafishTdgf1,and all threeXenopus EGF-CFCgenes (Tdgf1,Tdgf1.2andCripto.3) and are all descendants of the ancestralTdgf1gene. We propose that subsequent to the family expansion in tetrapods,Tdgf1B(Xenopus Tdgf1.2) acquired specialization in the left-right patterning cascade, and after its translocation in eutherians to a different chromosomal location,Cfc1/Cryptichas maintained that specialization.