THE DISTRIBUTION OF THE MATRICELLULAR PROTEIN THROMBOSPONDIN-2 IN TISSUES OF EMBRYONIC AND ADULT MICE

Mice that lack the matricellular protein thrombospondin 2 (TSP2) devel op a pleiotropic phenotype characterized by morphological changes in c onnective tissues, an increase in Vascular density, and a propensity f or bleeding. Furthermore, dermal cells derived from TSP2-null mice dis play adhesion defects, a finding that implicates TSP2 in cell-matrix i nteractions. To gain a better understanding of the participation of TS P2 in the development and maturation of the mouse, we examined its dis tribution in embryonic and adult tissues. Special attention was paid t o the presence of TSP2 in collagen fibers, because collagen fibrils in the TSP2-null mouse appear to be irregular in size and contour by ele ctron microscopy. Immunohistochemical analysis of Day 15 and Day 18 em bryos revealed TSP2 in areas of chondrogenesis, osteogenesis, and vasc ulogenesis, and in dermal and other connective tissue-forming cells. D istinctly different patterns of deposition of TSP2 were observed in ar eas of developing cartilage and bone at Days 15 and 18 of embryonic de velopment. A survey of adult tissues revealed TSP2 in dermal fibroblas ts, articular chondrocytes, Purkinje cells in the cerebellum, Leidig c ells in the testis, and in the adrenal cortex. Dermal fibroblasts were also shown to synthesize TSP2 in vitro. The distribution of TSP2 duri ng development is in keeping with its participation in the formation o f a variety of connective tissues. In adult tissues, TSP2 is located i n the pericellular environment, where it can potentially influence the cell-matrix interactions associated with cell movement and tissue rep air.