A non-transmembrane form of jagged-1 regulates the formation of matrix-dependent chord-like structures

Jagged-Notch interactions regulate a transmembrane ligand-receptor signalin g pathway involved in the regulation of cell. fate determination as well as myoblast and endothelial cell differentiation. To further examine the role of the transmembrane ligand, Jagged-1, in the regulation of cell different iation, we stably transfected NIH 3T3 cells with a truncated form of Jagged (J)-1, which results in the secretion of a soluble(s) form of the protein. Comparison of gene expression by serial analysis demonstrated that among th e 227 transcripts differentially regulated in the sJ-1 transfectants, the e xpression of the pro-alpha-2(I) collagen transcript and pro-alpha-1(I) coll agen translation product was predominantly repressed in sJ-1 transfectants. When plated on extracellular matrices, sJ-1 transfectants formed prominent chord-like structures on type I collagen but not on fibrin, fibronectin, o r vitronectin. While the sJ-1 transfectants exhibited growth kinetics simil ar to control cells and were unable to grow in soft agar, the cells were le ss sensitive to contact inhibition of growth in vitro and sJ-1 allografts f ormed tissue masses in nude mice after a prolonged latency period and exhib ited an abundance of host-derived microvascular endothelial cells. These da ta suggest that J-1 may be able to modulate, in a matrix-dependent manner, the organization of cell to cell interactions including its ability to prom ote the development of chord-like structures. (C) 2000 Academic Press.