Fig. 5

Integration of mechanical and biochemical signals at cranial sutures. In the developing calvaria, mesenchymal cells in the suture midline are proliferative and give rise to osteoprogenitors and osteoblasts in the osteogenic front. The calvaria sits on top of the dura mater and experiences a quasi-static tensile strain (blue arrows) due to the expansion of the growing brain underneath and the intracranial pressure. Such force then signals through FGF and IGF signaling to maintain mesenchymal cell proliferation, as well as TBX2 to inhibit GJA1 and premature differentiation. In the osteogenic front, tensile forces signal through BMP4 and Ca²⁺ influx to promote osteogenesis. α-adaptin C-dependent endocytosis also functions downstream of the tensile stress to promote osteogenic differentiation, possibly by enhancing BMP signals. Cyclic forces generated by masticatory muscle contraction promote both mesenchymal proliferation and osteogenic differentiation (red arrowheads), leading to suture widening