Figure 1

Inducible activation of β-catenin causes deficiencies in calvarial morphogenesis. (A) A schematic represents the strategy for targeted expression in the Axin2-expressing cells. Four day-old mice carrying Axin2-rtTA and TRE-lacZ transgenes without (B) or with (C) the Dox treatment, starting at E16.5, were analyzed for expression of the reporter. β-gal staining reveals strong expression of lacZ in the developing skull. Sections of the β-gal stained skulls at three different levels (D, internasal suture; E, metopic suture; F, sagittal suture) indicated in C exhibit targeted gene expression in the suture mesenchyme, osteogenic fronts (arrowheads), and periosteum (asterisks). (G) A scheme represents the development of a transgenic system, which integrates the tetracycline-dependent activation and Cre-mediated recombination, to express a degradation-deficient form of β-catenin (sβ-cat) in the Axin2-expressing cells. (H-J) Skeletal staining of control (H, genotype: Axin2-rtTA; β-cateninΔEx3Fx/+) and sβcat^Ax2 (I, J) mice reveals skull abnormalities caused by the expression of sβ-cat around P17. (K-P) H&E staining shows that conditional expression of sβ-cat expands metopic suture mesenchyme (K-M) and enhances bone ossification (N-P). The suture regions are enlarged in the sβcat^Ax2 mutants (L, M) compared to the control (K). Frontal bone volumes are increased in the sβcat^Ax2 skulls (O, P) compared to the control (N). Arrowheads indicate the osteogenic fronts. F, frontal bone; P, parietal bone. Scale bars, 2 mm (B, C, H-J); 200 μm (D-F, K-M); 100 μm (N-P).