RT Journal Article ID 066bba1806048ae4 A1 Fromigue, Olivia A1 Modrowski, Dominique A1 Marie, Pierre J. T1 Apoptosis in Membranous Bone Formation: Role of Fibroblast Growth Factor and Bone Morphogenetic Protein Signaling JF Critical Reviews™ in Eukaryotic Gene Expression JO CRE YR 2005 FD 2005-03-01 VO 15 IS 1 SP 75 OP 92 AB Membranous ossification occurs by the condensation of mesenchymal cells followed by their progressive differentiation into osteoblasts that form a mineralized matrix in ossification centers. The balance between proliferating and differentiated osteogenic cells at the suture areas between calvarial bones is essential for the control of suture maintenance and membranous bone formation. The mechanisms of regulation of cell apoptosis in suture areas begin to be understood. Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) are important regulators of mesenchymal, preosteoblast, and osteoblast apoptosis in suture areas. Perturbations in FGF or BMP signaling lead to alter the number of apoptotic osteogenic cells, resulting in premature or delayed suture closure. Recent data indicate that FGF signaling downregulates preosteoblast apoptosis, thereby preventing premature fusion of adjacent mineralizing extremities. In contrast, continuous FGF signaling or constitutive FGF receptor activation, as well as BMP signaling, upregulate osteoblast apoptosis. Additionally, multiple signaling mechanisms, including PI3K and PKC, appear to be involved in the control of calvarial osteoblast apoptosis by FGF and BMP. These mechanisms allow a fine control of the number of functional bone-forming cells and, thereby, the normal progression of membranous bone formation. PB Begell House LK https://www.dl.begellhouse.com/journals/6dbf508d3b17c437,03d0336f0e2ce096,066bba1806048ae4.html