Figure 4. Temporal and spatial expression of Bmp4 during tooth development is controlled by different domains of the Bmp4 gene. The upper panel depicts a schematic of the working hypothesis for control of Bmp4 expression during tooth development. Supporting data show that LacZ staining in Bmp4^lacZneo knock-in mice, representative of endogenous Bmp4 expression, first appears in the epithelium (A, 200x), followed by the mesenchyme and enamel knot (B, 200x), and then in the mature tooth cells such as pulp cells (C, 200x), odontoblast, and ameloblast cells (D, 40x). By contrast, panel E shows that LacZ stains from the Bmp4LacZ^2.4p mice are present only in the epithelium-derived ameloblasts. We propose that the Bmp4 gene region from –260 bp to –1.1 kb controls Bmp4 expression in the epithelium-derived ameloblasts, while Bmp4 expression in the mesenchyme-derived pulp cells and odontoblast cells is controlled by other regions. The control domains for Bmp4 expression in primordial tooth cells (PTC, see Fig 1 for more support data) are located in other regions of the Bmp4 gene, outside of the 2.4-kb Bmp4 gene area. Abbreviations: Am, ameloblast; Od, odontoblast; P, pulp cells.