DIFFERENTIAL EXPRESSION OF THROMBOSPONDIN-1, THROMBOSPONDIN-2, AND THROMBOSPONDIN-3 DURING MURINE DEVELOPMENT

Thrombospondin 1 is a secreted, trimeric glycoprotein that mediates in teractions between cells and extracellular matrix and exhibits cell-sp ecific effects on migration and proliferation. Recently, two additiona l thrombospondin genes (thrombospondin 2 and 3) have been identified. To study the functions of these proteins, we have used in situ hybridi zation and RNAse protection assays to compare the expression of the ge nes encoding thrombospondin 1, 2, and 3 during murine embryogenesis. T hrombospondin mRNAs were associated with ossification, neuronal organo genesis, and lung development, although transcripts were differentiall y expressed. Thrombospondin 1 was predominant from days 10 to 13. Duri ng this period, high but transient levels of expression were observed in the neural tube, head mesenchyme, and cardiac cushions. In contrast , a more constant level of thrombospondin 1 mRNA was apparent in resid ent megakaryocytes of the liver, as well as in circulating megakaryocy tes; neither thrombospondin 2 nor 3 was detected in these cells. Throm bospondin 1 was also produced by cells of the developing kidney and gu t. The expression of thrombospondin 2 was confined principally to orga nized connective tissue that included pericardium, pleura, perichondri um, periosteum, meninges, ligaments, and reticular dermis. Thrombospon din 2 was also produced by differentiating skeletal myoblasts and by c ells of the kidney and gut. Moreover, high levels of expression were d etected in blood vessels. Thrombospondin 3 mRNA was restricted to brai n, cartilage, and lung. Although thrombospondin 1, 2, and 3 belong to a family of structurally related genes, the differences observed in th e spatiotemporal distribution of the corresponding mRNAs indicate uniq ue functions for these secreted proteins. (C) 1993 Wiley-Liss, Inc.