Role of the EGF-CFC gene cripto in cell differentiation and embryo development.
The EGF-CFC proteins have been recently recognized as a novel family of extracellular factors required during early vertebrate development. Cripto is the founder member of the EGF-CFC family initially related to the epidermal growth factor (EGF); its expression is increased in human colon, gastric, pancreatic and lung carcinoma and in different types of both mouse and human breast carcinomas. Genetic studies in the mouse have established an essential role of cripto in the formation and correct positioning of the anterior-posterior axis. Furthermore, the absence of cripto results in a defective precardiac mesoderm, unable to differentiate into functional cardiomyocytes. Although mouse and human Cripto have been shown to activate the ras/raf/MAP kinase pathway in mammary epithelial cell lines, genetic evidence in Zebrafish has been provided for a relationship between the EGF-CFC proteins and Nodal, a member of the transforming growth factor family. Here we review the biological role of cripto in development and differentiation, pointing out recent findings on the biochemical interactions of Cripto, Nodal and Activin-like receptors.
Minchiotti
Gabriella
G
International Institute of Genetics and Biophysics, CNR, Via Marconi 12, 80125 Naples, Italy. minchiot@iigb.na.cnr.it
Parisi
Silvia
S
Liguori
Giovanna L
GL
D'Andrea
Daniela
D
Persico
M Graziella
MG
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D004815:Epidermal Growth Factor; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D029961:Zebrafish Proteins
D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human; C489450:Tdgf1 protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; C110484:tdgf1 protein, zebrafish; D004815:Epidermal Growth Factor