THROMBOSPONDIN-4 IS EXPRESSED BY EARLY OSTEOGENIC TISSUES IN THE CHICK-EMBRYO

The thrombospondins are a family of related glycoproteins found in the embryonic extracellular matrix. To date, five members of this family have been identified. Thrombospondin-1 and thrombospondin-2 have simil ar primary structure, but are expressed in different tissues at differ ent times during development. Thrombospondins-3, -4, and cartilage oli gomeric protein belong to a second thrombospondin subgroup in which th e carboxyl-half of each molecule is most similar to thrombospondin-1 a nd -2. Here, we report the cloning and sequencing of a novel probe to avian thrombospondin-4. We have used this probe to determine the origi ns of thrombospondin-4 in the chick embryo by in situ hybridization. T hrombospondin-4 transcripts first appear in the mesenchyme surrounding bone anlage coinciding with the initial stages of osteogenesis. The e xpression in osteogenic tissues is transient: thrombospondin-4 mRNAs a re not seen in the osteoblasts of bone collars in developing long bone s. This pattern is distinct from avian thrombospondin-2, which is expr essed in perichondrium and embryonic fibrous connective tissues. Our o bservations indicate that connective tissues are the principal site of thrombospondin-4 expression in the chick. The diverse origins of diff erent thrombospondin gene family members imply distinctive roles for t hese proteins related to the growth and differentiation of cartilage, tendons, and bone. (C) 1995 Wiley-Liss, Inc.