[Growth pattern of the frontal bone primordium and involvement of Bmps in this process]

The mammalian skull vault consists of several membrane bones with different origins. A pair of frontal bones, which occupies the anterior part of the skull vault, is derived from cranial neural crest cells. The frontal bone primordium develops at the superciliary ridge region, then expands towards the top of the head. In this study, we investigated the growth pattern of the frontal bone primordium and the factors involved in this process. In situ hybridization of fibroblast growth factor receptor 2 and Runx2, which are markers of preosteoblast, revealed that the frontal bone primordium appears around embryonic day 12.5 (E 12.5) and actively grows between E 14 and E 16. We labelled the head mesenchyme of E 13 at the superciliary ridge with DiI by ex-utero surgery and found that the labelled cells were present at the apical edge of the developing frontal bone on E 18. To elucidate the molecular basis of this formation, we cultured E 15 calvarium in the presence of recombinant human bone morphogenetic proteins (rhBMPs); rhBMP-2 and rhBMP-7, but not rhBMP-4, accelerated the growth of the frontal bone domain. These results suggest that the frontal bone primordium grows intrinsically by expanding the primordium not by recruiting surrounding cells, and Bmp-2 and -7 play roles in stimulating the growth of the frontal bone primordium.