Fig. 6. A schematic model suggesting how NFB, Id1 and possibly Twist may interact to control FGFR gene expression. In this hypothetical scheme, it is proposed that the feedback regulation of FGFR expression in RCS cells involves principally NFB and Id, acting via an unknown intermediary factor, which may be a b-HLH protein such as (Twist). Activation of FGFR induces upregulation of NF-B subunits NF-B1 (p50/p105) and RelA(p65) (Ghosh et al., 1998) and downregulation of Id1, a general inhibitor of terminal differentiation, which was shown to inhibit Twist by direct interaction with the protein. Several studies have demonstrated that activated NF-B can upregulate Twist protein either directly or through inhibition of BMP4 signaling, which can directly regulate the expression of Id1. Since the involvement of Twist in this cell system is unknown and hypothetical, it has been placed in parentheses. FGFR may also downregulate the expression of Id1 via a NF-B-independent signaling pathway. Both downregulation and signaling shut-off of FGFR3 are tightly regulated during chondrocyte maturation and terminal differentiation. `FGFR3' refers to the total signal-transduction activity mediated via FGFR3, determined by the sum of activated FGFR3 molecules in the cell. The left side of the figure denotes alterations in chondrocyte morphology and their correlation with FGFR3 activity. Initially, FGFR3 signalling level is high and is associated with a transition in chondrocyte morphology from a polygonal to a rounded shape. In the last stage of the process (bottom cell), FGFR3 is downregulated and its signaling activity ceases as the cells attain a fully rounded shape.