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Subtractive hybridization identifies chick-cripto, a novel EGF–CFC ortholog expressed during gastrulation, neurulation and early cardiogenesis
Ist Teil von
Gene, 2000-09, Vol.255 (2), p.205-217
Ort / Verlag
Netherlands: Elsevier B.V
Erscheinungsjahr
2000
Quelle
Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)
Beschreibungen/Notizen
EGF–CFC genes encode a novel class of extracellular, membrane-associated proteins that notably play an important role during vertebrate gastrulation. Whereas the two cysteine-rich domains that characterize these proteins, namely the extracellular EGF-like and the CFC domain, are known to be encoded by two evolutionarily conserved exons, it is generally assumed, based on weak primary sequence identity, that the remaining parts of the protein differ among vertebrates, suggesting that known members of the EGF–CFC family do not represent true orthologs. Here, by characterizing the full cDNA and genomic sequences of a new
EGF–CFC gene in chick, and by comparing them with their counterparts in human (
CRIPTO), mouse (
cripto and
cryptic),
Xenopus (
FRL-1) and zebrafish (
one-eyed pinhead), we show that all
EGF–CFC genes share an identical genomic organization over the entire coding region. Not only are the central two exons (coding for the EGF-like and CFC motifs) conserved, but also conserved are the total number of exons, their size, their intron phase and their correlation with discrete protein modules, in particular those modules that allow the EGF–CFC motif to become membrane-associated. Therefore, despite apparent divergence between their 5′ and 3′-terminal exons, all known
CRIPTO-related genes are structurally orthologous. We named this novel ortholog in bird,
chick-cripto. We report the mRNA distribution of
chick-cripto, which begins in the epiblast of the gastrula, with a pattern similar to
EGF–CFC genes of other vertebrates.