int-1--a proto-oncogene involved in cell signalling

The int-1 gene was originally identified as a locus activated by mouse mammary tumor virus insertion. Cloning and sequencing of the mouse gene indicates that int-1 encodes a 41K, 370 amino acid, cysteine-rich protein with a potential hydrophobic signal peptide sequence. Expression studies clearly indicate that int-1 enters the secretory pathway and is probably secreted, although definitive evidence is lacking. Drosophila int-1 encodes the wingless gene, wingless, a segment-polarity gene, is required for the establishment of normal pattern in each segment. Genetic studies indicate that the wingless protein is probably secreted since it is required for the maintenance of stable gene expression in neighboring cells. int-1 is also expressed during early neural stages of frog and mouse development. In the mouse, where expression is well characterized, int-1 RNA is restricted to the dorsal midline of the neural tube. By analogy with Drosophila, int-1 may operate to specify position within this structure. To test this idea, we have interfered with normal int-1 expression by injection of int-1 RNA into frog embryos. This results in a striking and specific aberration, bifurcation of the anterior neural tube. Thus, it seems possible that in vertebrates int-1 is able to influence patterning events.