Figure 5.

The nonendochondral fate of Meckel's cartilage (MC) is MT1-MMP dependent. (A–F) Wild-type mouse. (G–K) MT1-MMP–deficient mice. In wild-type mice (A and B), MC is conspicuous at E16.5. The rostral portion of MC (A, black arrows) undergoes hypertrophy and endochondral ossification, while the midportion (A, white arrow) is replaced by membranous bone, and its posterior portion (A, gray arrow) by the sphenomandibular ligament (detailed view of MC [arrows], malleus [m], and incus [i] shown in B). Both processes are completed in the wild-type mouse by day 5, when only small residual portions of MC can be observed after thorough sectioning of the mandible (C, arrows). The nonbasophilic peripheral portions of these islands contain multiple apoptotic chondrocytes (D, arrows). MT1-MMP mRNA (E and F, arrows) is expressed in chondrocytes residing in the dissolving matrix next to the mandibular bone (E and F, mb). Extensive remnants of MC are retained in 6-d-old MT1-MMP–deficient mice (G–K, black and white arrows), and older. MC remnants have lost basophilia (proteoglycan content), and significant numbers of chondrocytes, thus appearing as a ghost cartilage with multiple empty chondrocyte lacunae, best seen in I (mc). (G) Sagittal section of the hemi-mandible demonstrating molars (m), MC (black and white arrows), and mandibular bone (mb). (H–K) Coronal sections through the mouse skull. I and K are higher magnification views of MC remnants shown in H and J. t, tongue; i, lower incisor; m, mandible; mc, Meckel's cartilage; n, nerve. (A–B) Whole-mount alcian blue staining. (C, E, G–K) Hematoxylin and eosin (H&E)–stained sections. (D) TUNEL staining. (F) In situ hybridization for MT1-MMP. Bars: (A) 1 mm; (B) 0.5 mm; (C–G, and K) 100 μm; (I) 40 μm; (H and J) 200 μm.