Worm Breeder's Gazette 12(4): 30 (October 1, 1992)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Sequence Analysis of a C. elegans Member of the tolloid/BMP1 Family

Alyce L. Finelli[1], Monica Driscoll[2], Richard W. Padgett[1]

Figure 1

Figure 2

[1]Waksman Institute
[2]Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855

tolloid is crucial for proper pattern formation along the dorsal-ventral axis in the early Drosophila embryo, in addition to having a functional role in development of disks and the brain. During early embryonic patterning, tolloid genetically interacts with decapentaplegic (dpp), a growth factor member of the TGF-b family. The members of this large family of secreted peptide growth factors are molecules with diverse regulatory activities, including stimulation and/or inhibition of cell growth or differentiation, and control of cell fate. The activity of these growth factors is altered by proteins which interact with them and modulate their activity. Such a role is postulated for tolloid and

BMP1 .

The members of the tolloid/BMP1 family share a similar structure; they all contain a novel metalloprotease domain, EGF repeats, and repeats found in the complement proteases (Clr/s repeats). This ancient family of metalloproteases, which has members in sea urchins, insects, vertebrates, and now nematodes, has been implicated in a variety of developmental processes. The presence of EGF and Clr/Cls repeats suggests these metalloproteases form regulatory interactions with other proteins. Thus, they are members of a family of conserved proteases involved in cell determination, developmental, and differentiation processes.

A recently isolated clone, cm01 A12,localized to cosmid T24A11 on the third chromosome, displayed significant similarity to the protease domain of tolloid and BMP-1 (Waterston et al., 1992, Nature Genetics 1:114-123) [SeeFigure 1]. Since we suspected this clone might be a member of the tolloid/BMP1 metalloprotease family, we analyzed the sequence of several cDNAs. This analysis revealed the presence of EGF and Clr/s repeats (data not shown). Hence, this gene is a member of the tolloid/BMP1 family of regulatory metalloproteases [See Figure 2]. Its presence in the worm further reinforces the idea that TGF-b like molecules exist in this organism.

The cm01 A12gene represents the only other member of this family identified in a genetically tractable organism. Our plans include identifying mutations in the gene, and examining its expression. This may elucidate the pathway(s) through which this protein functions, and may identify other genes involved. [See Figure 1&2;]

Literature Cited:

Waterston et al., 1992, Nature Genetics 1:114-123.

Figure 1

Figure 2