Interactions of Ihh and PTHrP signaling pathways in the fetal growth plate. This figure shows a schema of the fetal growth plate of the mouse long bone. The end of the bone is at the top. As proliferating chondrocytes differentiate into prehypertrophic chondrocytes and then hypertrophic chondrocytes, they express Ihh. Ihh directly or indirectly stimulates PTHrP synthesis in the periarticular growth plate including the perichondrium and periarticular proliferating chondrocytes (long solid arrow). In this way, Ihh signals the relative position of prehypertrophic and hypertrophic chondrocytes to the periarticular growth plate. Ihh also has a positive effect on chondrocyte proliferation (short solid arrow). PTHrP then acts directly on columnar proliferating chondrocytes to delay their differentiation into prehypertrophic and hypertrophic chondrocytes, which synthesize Ihh (solid t-bar). Thus, through PTHrP, Ihh controls the site at which hypertrophy occurs. Ihh also acts on perichondrial cells to induce mature osteoblasts, which form a bone collar (white arrow).