Fig. 8. The hypothesized roles of regulatory genes during limb development. (A) The expression patterns of genes that regulate DV patterning of the limb ectoderm. This schematic depicts a transverse section of the limb bud with proximal to the left, distal to the right ending in the AER, and dorsal towards the top. (B) Model for the genetic pathway regulating dorsal/ventral patterning of the limbs. As shown in this study, Bmpr signaling in the limb ectoderm is required for En1 gene expression (red in A) in the ventral ectoderm. Previous studies have demonstrated a role for En1 in suppressing the expression of Wnt7a (yellow) in ventral ectoderm (Cygan et al., 1997; Loomis et al., 1996; Loomis et al., 1998), thereby restricting its expression to the dorsal ectoderm. Wnt7a has been shown to induce the expression of Lmx1b (blue) in the mesoderm underlying the dorsal ectoderm (Cygan et al., 1997; Loomis et al., 1998; Riddle et al., 1995). Figure adapted and modified from Johnson and Tabin (Johnson and Tabin, 1997). (C) Hypothesized molecular mechanisms that dictate DV patterning in the presumptive limb region before limb bud formation and the presumptive fate maps of limb ectoderm. Ventral embryonic regions that express Bmp4 are depicted in various shades of blue with lateral mesoderm (lm) depicted as the darkest shade of blue, and intermediate mesoderm (im) with lighter blue shading. Somitic mesoderm (so) is depicted as red, in those regions that express noggin, and as orange in the remainder of the somite. In the ectoderm, purple denotes regions that correspond to chick ectoderm previously fate mapped to form dorsal limb ectoderm (Altabef et al., 1997; Michaud et al., 1997). Green denotes regions fated to contribute to ventral ectoderm. The arrowhead denotes the boundary between the dorsal and ventral limb compartments (Altabef et al., 1997; Michaud et al., 1997). Our model hypothesizes that the expression of BMPs in the ventral and lateral mesoderm (blue) induce the ventral identity of the overlying ectoderm (green). This induction is blocked by noggin expression in the somite, which previously has been shown to express noggin (Capdevila and Johnson, 1998; Hirsinger et al., 1997; Marcelle et al., 1997; McMahon et al., 1998; Reshef et al., 1998; Tonegawa and Takahashi, 1998). In addition, this region has been demonstrated to induce the overlying ectoderm to form dorsal limb ectoderm (Michaud et al., 1997). Our model proposes that the inhibition of BMP induction in ectoderm overlying the most medial parts of the lateral mesoderm (where purple ectoderm overlies blue mesoderm) is accomplished by noggin. The region of ventral ectoderm hypothesized in this model corresponds to the domain of Msx2 gene expression, which is lost in the Bmpr mutant. (D) Schematic illustration of morphogenetic movements of ectoderm to form dorsal limb ectoderm (purple), AER (yellow) and ventral ectoderm (green).
