Fig. 7. Summary of experimental results and a model for the role of mesenchyme in regulating mandibular osteogenesis via BMP signaling. (A) The HH staging system operates independently of time, and instead is based on external morphological characters. Thus, quail and duck can be aligned at equivalent points during development by incubating them for prescribed lengths of time. Internal events such as Bmp4 expression and osteoid matrix deposition occur at equivalent stages in quail and duck but are accelerated on the donor side of quck relative to the duck host. (B) Neural crest-derived mesenchyme (dark gray) migrates from the midbrain and hindbrain around HH9.5 and settles in the mandibular primordia by HH15 (Tosney, 1982; Noden, 1991). During this early period, they establish the timing of interactions required for bone formation by signaling to adjacent epithelium (black arrows). Simultaneously, the epithelium is expressing growth factors such as Bmp4 (blue arrows) and other genes (light gray arrows) that support autonomous progression of mesenchymal regulatory programs. (C) At HH23, epithelium continues to express Bmp4 (blue domain) and other factors that enable mesenchymal cells to continue outgrowth. (D) By HH25, Bmp4 expression transitions from epithelium to mesenchyme. Mesenchymal expression of Bmp4 is auto-regulatory (black arrows), but requires permissive signals from epithelium. (E) By HH27, epithelium is no longer required to maintain Bmp4 expression and mesenchyme autonomously differentiates into bone.