Fig. 9. A genetic model for dorsal/ventral pharyngeal arch patterning. Two edn1 downstream target genes, bapx1 (red) and hand2 (green), specify joints and ventral pharyngeal fates, respectively. edn1 is also required for the second arch joint, which is bapx1-independent, so an additional arrow is drawn from edn1 to joint fates. The early ventral expression of msxe, dlx3, gsc and EphA3 requires edn1 but not hand2. The later (38 hpf, see Fig. 7H,I) arch one ventral, but not the early arch two ventral, gsc expression requires both hand2 and edn1. In the first arch, hand2 represses the expression of dorsally restricted eng2 and joint-restricted bapx1. bapx1 positively regulates gdf5 and chd, potential effectors of jaw joint development. Although both edn1 and hand2 repress eng2, we parsimoniously propose this is through hand2. We propose the role of dlx2 in patterning the dorsal pharyngeal arches is conserved between mice (Qiu et al., 1995; Qiu et al., 1997; Panganiban and Rubenstein, 2002) and zebrafish. In zebrafish, dlx2 appears to be expressed throughout the entire postmigratory cranial neural crest (CNC) cylinder (Miller et al., 2000; Kimmel et al., 2001a; Kimmel et al., 2001b). The ventral subdomain of dlx2 expression which requires edn1 function (Miller et al., 2000) also appears to require hand2 function (data not shown), not diagrammed here for simplicity. dlx6 helps transduce the Edn1 signal to hand2 in mice (Charité et al., 2001) (also not shown here). Proposed functions not yet experimentally tested are indicated by broken lines. The dorsoventral pharyngeal arch axis in tetrapods is sometimes referred to as the proximal-distal axis.