Drosophila Genes in Development: Dorsal-ventral polarity
tolloid is intimately involved in the process of dorsal-ventral polarity in Drosophila. The major effector protein molecule in D-V patterning is Decapentaplegic (DPP). DPP is synthesized in an inactive form and therefore requires enzymatic proteolysis for its activation. Undergoing proteolysis allows DPP to become active.
Tolloid protein contains a metalloprotease, and is therefore, a candidate for DPP proteolysis.
Evidence for a physical interaction between TLD and DPP comes from the observation that certain tld alleles fail to complement a partial loss-of-function dpp allele. These alleles produce aberrant products that form nonfunctional complexes with DPP protein (Ferguson E. L., 1994).
Tolloid exhibits a complex structure consisting of an N-terminal domain with sequence similarity to the astacin family of metalloproteases and a C-terminal domain composed of two EGF-like repeats and five copies of the CUB repeat which was first found in human complement proteins C1r and C1s. The overall structure of TLD is similar to the human bone morphogenetic protein, BMP-1. The tld sequence is 41% identical to human BMP-1 (Shimell M.J., 1991).
Extracellular
tld transcripts are observed in 0-12 hr embryos on northern blots. Transcripts are first detected by in situ hybridization at nuclear cycle 10-11 in dorsally located nuclei in the central portion of the embryo and in dorsally and ventrally positioned nuclei at the poles. The first alternation is a reduction in the staining of the cells located within 10% egg length from each pole. With further reduction, four distinct bands of expression are observed by the end of cellularization. The dorsal-most 10-20% of the embryo's circumference becomes more heavily stained (Shimell M.J., 1991).
tld expression is observed in three lateral patches of cells in the emerging gnathal segments and more weakly in patches of cells in more posterior segments. During stages 10 and 11, two parallel groups of labelled cells arise. One comprises a continuous stripe of cells located between the dorsal epidermis and the amnioserosa, and a second is compared to segmentally repeated cells near the boundary between dorsal epidermis and the neurogenic region, around the tracheal pits (Shimell M.J., 1991).
Pair-rule
HOX-Pro