Localization and Roles of Hepatocyte Growth Factor (HGF) in Development and Disappearance of Mouse Meckel's Cartilage

[Abstract] : Hepatocyte growth factor (HGF) was originally identified as a potent mitogen for liver parenchymal cells and is substantially expressed in the first branchial arch of mouse embryos. The present study aimed to investigate immunohistochemically the localization of and changes in the expression of HGF and c-Met, a specific receptor for HGF. Further we determined the developmental roles of HGF in mouse Meckel's cartilage by using an organ-culture system and NK4, an antagonist of HGF. Both HGF and c-Met were co-localized in proliferating chondrocytes, suggesting their autocrine/paracrine roles in Meckel's cartilage of embryonic mice. In hypertrophic chondrocytes adjacent to the resorption portions, the expression of both HGF and c-Met was diminished. Supplementation with HGF enhanced the length of Meckel's cartilage, whereas the diameter of the cartilage was not affected, in organ-culture experiments. NK4 induced hypertrophy of Meckel's chondrocytes, which was accompanied by the expression of type X collagen and alkaline phosphatase activity. These results strongly suggest that HGF plays important roles in the characteristic slender morphogenesis of Meckel's cartilage by promoting chondrocyte migration and that down-regulation of HGF/c-Met induces hypertrophy and subsequent resorption of Meckel's cartilage.