Experimental evidence indicates that the mandibular primordia are specified as at least two independent functional regions: two large lateral (proximal) regions where morphogenesis is dependent on FGF-8 signaling, and a small medial region where morphogenesis is independent of FGF-8 and dependent on other signals. The patterns of expression of multiple signaling molecules and regulatory genes in the epithelium and mesenchyme of the medial region suggest that the regulatory hierarchies controlling morphogenesis of the medial region of the developing mandible are complex and involve multiple pathways. Recent genetic studies indicate that the ‘ET-1-dHAND-Msx1 pathway’ constitutes one of the genetic pathways involved in outgrowth and morphogenesis of the medial region. Functional studies in chick mandible suggest that FGFs (other then FGF-8) and BMPs are also part of signaling pathways that regulate morphogenesis of the medial region. These studies suggest that in the medial region of the developing mandible, FGF-mediated signaling is involved in growth-promoting interaction, whereas BMP-mediated signaling is involved in chondrogenesis.

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