GON-1 and fibulin have antagonistic roles in control of organ shape

Curr Biol. 2004 Nov 23;14(22):2005-10. doi: 10.1016/j.cub.2004.11.006.


Most developing organs are surrounded by an extracellular matrix (ECM), which must be remodeled to accommodate growth and morphogenesis. In C. elegans, the GON-1 ADAMTS metalloprotease regulates both elongation and shape of the developing gonad . Here, we report that either human ADAMTS-4 or ADAMTS-9 can substitute for GON-1 in transgenic worms, suggesting functional conservation between human and nematode homologs. We further identify fibulin (FBL-1), a widely conserved ECM component , as critical for gonadal morphogenesis. FBL-1 is expressed in nongonadal tissues but is present at the surface of the elongating gonad. A fibulin deletion mutant has a wider than normal gonad as well as body size defects. We find that GON-1 and fibulin have antagonistic roles in controlling gonadal shape. Depletion of fbl-1, but not other ECM components, rescues gon-1 elongation defects, and removal of gon-1 rescues fbl-1 width defects. Therefore, the GON-1 protease normally promotes tissue elongation and expansion, whereas the fibulin ECM protein blocks these key morphogenetic processes. We suggest that control of organ shape by GON-1 and fibulin in C. elegans may provide a model for similar cellular processes, including vasculogenesis, in humans.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins
  • ADAMTS4 Protein
  • ADAMTS9 Protein
  • Animals
  • Animals, Genetically Modified
  • Blotting, Western
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Gene Expression Regulation, Developmental*
  • Gonads / embryology*
  • Gonads / metabolism
  • Humans
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Models, Biological
  • Morphogenesis / physiology*
  • Mutation / genetics
  • Phylogeny
  • Procollagen N-Endopeptidase
  • RNA Interference


  • Caenorhabditis elegans Proteins
  • Calcium-Binding Proteins
  • fibulin
  • ADAM Proteins
  • ADAMTS9 Protein
  • ADAMTS9 protein, human
  • GON-1 protein, C elegans
  • Metalloendopeptidases
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein
  • ADAMTS4 protein, human