DISTINCT SPATIAL AND TEMPORAL EXPRESSION PATTERNS OF 2 TYPE-I RECEPTORS FOR BONE MORPHOGENETIC PROTEINS DURING MOUSE EMBRYOGENESIS

Bone morphogenetic proteins (BMPs) are multifunctional proteins struct urally related to transforming growth factor-beta (TGF beta) and activ in that can induce cartilage and bone growth in vivo. Members of the T GF beta superfamily exert their biological effects via heteromeric ser ine/threonine kinase complexes of type I and type II receptors. We pre viously obtained six different type I receptors, termed activin recept or-like kinase-1 (ALK-1) to -6. ALK-5 is a TGF beta type I receptor, A LK-2 and ALK-4 are activin type I receptors, and ALK-3 and ALK-6 are t ype I receptors for osteogenic protein-1 (OP-1)/bone morphogenetic pro tein-7 (BMP-7) and BMP-4. Here we report the complementary DNA cloning of the mouse homolog of ALK-3, which is highly conserved between mous e and man. ALK-3 messenger RNA (mRNA) is ubiquitously expressed in var ious adult mouse tissues, whereas ALK-6 mRNA is only found in brain an d lung. The distribution of ALK-3 and ALK-6 mRNA in the postimplantati on mouse embryo [6.5-15.5 days postcoitum (pc)] was studied by in situ hybridization. ALK-3 was nearly ubiquitously expressed throughout the se stages of development, but was notably absent in the liver. In cont rast, ALK-6 showed a more restricted expression pattern. ALK-6 mRNA wa s absent in early postimplantation embryos, was detected first in 9.5 days pc embryos, and persisted until 15.5 days pc. In midgestation emb ryos, ALK-6 transcripts were detected in mesenchymal precartilage cond ensations, premuscle masses, blood vessels, central nervous system, pa rts of the developing ear and eye, and epithelium. The expression in s ites of developing cartilage and bone supports the idea that ALK-3 and -6 are receptors for BMPs in vivo. In addition, the expression of the se genes in many soft tissues suggests broader functions for BMPs in e mbryogenesis.