SCREENINGVERFAHREN VON MORPHOGENISCHEN PROTEINEN

摘要

The invention provides a method of identifying a tissue source of epithelial cells that express a cellular gene encoding a polypeptide, the amino acid sequence of which comprises (I) a sequence having at least 70% amino acid sequence homology with the C-terminal seven-cysteine domain of human OP-1, residues 38-139 of SEQ ID No. 5, or (II) a sequence defined by generic sequence 6, SEQ ID No. 31, said polypeptide, when dimerized with a second said polypeptide, forming a protein having the property of inducing a developmental cascade of tissue-specific morphogenesis in a mammal, said method further being a method of screening a candidate compound for the ability to modulate expression of said gene, said method comprising the steps of: (a) incubating at least two preparations comprising epithelial cells derived from at least two different tissues of an organism with a compound shown to modulate expression of said gene for a time sufficient to allow said compound to affect the expression of said gene; (b) assaying said at least two preparations of cells for the presence or amount of an expression product of said gene, wherein a change in the level of said expression product relative to the level thereof in said at least two preparations of cells in the absence of said compound identifies cells wherein a change occurred as a tissue source of epithelial cells suitable for screening a candidate compound for the ability to modulate expression of said gene; (c) incubating said candidate compound with epithelial cells cultured from the tissue source for which a change in the level of gene expression was observed in step (b), for a time sufficient to allow said candidate compound to affect the expression of said gene; and (d) assaying said cultured epithelial cells for the presence or amount of an expression product of said gene, wherein a change in the level of said expression product relative to the level thereof in said cultured epithelial cells in the absence of said candidate compound is indicative of the ability of said compound to modulate expression of said gene in said cultured epithelial cells.