Fgf and Bmp signals repress the expression of Bapx1 in the mandibular mesenchyme and control the position of the developing jaw joint

The development of the jaw joint between the palatoquadrate and proximal part Meckel's cartilage (articular) has recently been shown to involve the gene Bapxl. Bapxl is expressed in the developing mandibular arch in two distinct caudal, proximal patches, one on either side of the head. These domains coincide later with the position of the developing jaw joint. The mechanisms that result in the restricted expression of Bapxl in the mandibular arch were investigated, and two signaling factors that act as repressors. were identified. Fibroblast growth factors (Fgfs) expressed in the oral epithelium restrict expression of Bapxl to the caudal half of the mandibular arch, while bone morphogenetic proteins (Bmps) expressed in the distal mandibular arch restrict expression of Bapxl to the proximal part of the mandible. Application of Fgf8 and Bmp4 beads to the proximal mesenchyme led to loss of Bapxl expression and later fusion of the quadrate and articular as the jaw joint failed to form. In addition to fusion of the jaw joint, loss of Bapxl lead to loss of the retroarticular process (RAP), phenocopying the defects seen after Bapxl function was reduced in the zebrafish. By manipulating these signals, we were able to alter the expression domain of Bapxl, resulting in a new position of the jaw joint. (C) 2003 Elsevier Inc. All rights reserved.