The growth and morphogenesis of the early mouse mandible: a quantitative analysis.

Three-dimensional reconstruction and BrdU incorporation have been used to quantify the development and growth of the mouse mandible and to analyse its relationship to Meckel's cartilage and the molar teeth. The mandible anlage is first histologically detectable at E13.5 as paired plates of osteoid tissue within condensed mesenchyme (approximately 0.9 mm long and approximately 0.36 mm deep) that are lateral to the two arms of Meckel's cartilage. Over the next 3 days, each plate lengthens to approximately 3.6 mm, and extends medially at its superior and inferior edges, folding over to enclose the alveolar nerve and Meckel's cartilage and producing additional processes that form the molar tooth sockets (E15.5). At around E15.5, the first molar tooth socket forms from two processes that extend from the medial and distal parts of the mandible to surround the tooth. By E16.5, this process is complete in the distal region where Meckel's cartilage is beginning to degenerate. Mandible ossification begins at E14 with proliferation restricted to the outer surface. BrdU incorporation rates are particularly high at the proximal and distal ends where lengthening occurs, and at the superior and inferior edges as they extend medially to surround Meckel's cartilage. Incorporation rates slow at the distal ends of each mandible at E16.5 as they approach each other at the symphysis. The results indicate that the mandible mainly grows at its periphery, and the pattern of mandibular growth and morphogenesis suggests that these processes are mainly directed and constrained by paracrine signalling from Meckel's cartilage and the tooth buds.