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Control of organ shape by a secreted metalloprotease in the nematode Caenorhabditis elegans

Nature volume 399, pages 586–590 (1999)Cite this article

Abstract

The molecular controls governing organ shape are poorly understood. In the nematode Caenorhabditis elegans, the gonad acquires a U-shape by the directed migration of a specialized ‘leader’ cell, which is located at the tip of the growing gonadal ‘arm’1. The gon-1 gene is essential for gonadal morphogenesis: ingon-1 mutants, no arm elongation occurs and somatic gonadal structures are severely malformed2. Here we report that gon-1 encodes a secreted protein with a metalloprotease domain and multiple thrombospondin type-1-like repeats. This motif architecture is typical of a small family of genes that include bovine procollagen I N-protease (P1NP), which cleaves collagen3, and murine ADAMTS-1, the expression of which correlates with tumour cell progression4. We find that gon-1 is expressed in two sites, leader cells and muscle, and that expression in each site has a unique role in forming the gonad. We speculate that GON-1 controls morphogenesis by remodelling basement membranes and that regulation of its activity is crucial for achieving organ shape.

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Figure 1: The gon-1 gene is required for morphogenesis of the gonad.
Figure 2: The gon-1 gene and protein.
Figure 3: The gon-1 promoter drives GFP expression in leader cells and in muscle.
Figure 4: gon-1 expression is critical for organ shape.

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Acknowledgements

We thank A. Coulson for providing cosmids, R. Barstead and A. Puoti for cDNA libraries, A. Fire for GFP and expression vectors, D. Gao for lag-2 promoter, J. Nance for Tc1 primers, theCaenorhabditis Genetics Center for worm strains, and the many lab members who provided thoughts and criticisms during the course of this work. R.B. is an MD/PhD student and was an NIH Molecular Biosciences trainee. J.K. is an investigator with the Howard Hughes Medical Institute and has been supported by grants from NIH and NSF.

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  1. Program in Cell and Molecular Biology, University of Wisconsin-Madison, Madison, 53706, Wisconsin, USA

    Robert Blelloch

  2. Howard Hughes Medical Institute, and Departments of Biochemistry, University of Wisconsin-Madison, Madison, 53706, Wisconsin, USA

    Judith Kimble

  3. Medical Genetics and Laboratory of Molecular Biology, University of Wisconsin-Madison, Madison, 53706, Wisconsin, USA

    Judith Kimble

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  1. Robert Blelloch
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Correspondence to Judith Kimble.

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Blelloch, R., Kimble, J. Control of organ shape by a secreted metalloprotease in the nematode Caenorhabditis elegans. Nature 399, 586–590 (1999). https://doi.org/10.1038/21196

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