CHARACTERIZATION OF TOLLOID-RELATED-1 - A BMP-1-LIKE PRODUCT THAT IS REQUIRED DURING LARVAL AND PUPAL STAGES OF DROSOPHILA DEVELOPMENT

The Drosophila tolloid (tld) gene product belongs to a family of devel opmentally important proteins that includes bone morphogenetic protein -1 (BMP-1). In Drosophila, tld is required at the blastoderm stage to establish pattern within the dorsal half of the embryo. Genetic analys is suggests that the major function of tld is to augment the activity of the decapentaplegic gene product, a close relative of the TGF-P sup erfamily members, BMP-2 and BMP-4. In this report, we describe a new g ene called tolloid-related-1 (tlr-1) that maps immediately proximal to tld. Sequence analysis indicates that tlr-1 has a large N-terminal ex tension relative to tld, but otherwise shows the same general organiza tion of sequence motifs found in tld and other BMP-1 family members. T hese include a region of similarity to astacin, a crayfish metalloprot ease, five copies of a repeat first found in complement proteins Clr a nd Cls, and two copies of an epidermal growth factor-like sequence. In situ hybridization experiments show that tlr-1 expression partially o verlaps tLd expression in early embryos, but shows unique transcriptio nal patterns in late stage embryos that are not seen with tld. In larv al stages, both genes are expressed in identical patterns in imaginal discs and in the optic lobes of the brain, but tlr-1 is more abundant than tld. Deletions that eliminate tlr-1 expression cause lethality du ring larval and pupal stages of development. A small proportion of hom ozygous mutant flies eclose and show wing veination defects. Transgeni c animals in which a tlr-1 cDNA is driven by the tld promoter fail to rescue tld mutations, and extra copies of tld fail to rescue tlr-1 mut ations, implying that these genes have evolved functionally distinct f eatures. We propose that tld and tlr-1 arose by gene duplication and t hat each has evolved independently to acquire distinct tissue specific roles in Drosophila development. (C) 1994 Academic Press, Inc.