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Fig. 10. Fgf3- and Fgf8-dependent and -independent pathways for otic development. Model to summarize potential interactions between hindbrain Fgf signals and otic placode transcription factors. (Top) Fgf3 and Fgf8 (FGF) are expressed at high levels by hindbrain rhombomere 4 (Maves et al., 2002; Walshe et al., 2002). Adjacent rhombomeres are labeled R5 and R6. (Middle) Cells of the presumptive otic placode express sox9b and the three transcription factors deleted by the Dfb380 mutation: dlx3b, dlx4b and sox9a (Fig. 1). Both sox9a (Fig. 6A-D) and to some extent sox9b (Fig. 6E-H) require Fgf signaling, whereas dlx3b (Fig. 6I-L) and dlx4b do not. dlx3b and sox9a crossregulate each other's expression in the placode (Fig. 8C-F) and dlx3b and dlx4b regulate sox9b (Fig. 8I,J). Thus, interactions between the Fgf3- and Fgf8-dependent factor, sox9a, and the relatively Fgf3- and Fgf8-independent factors (sox9b, dlx3b and dlx4b) are required for formation of the epithelium of the otic vesicle (bottom) and subsequent differentiation of the inner ear.