title: GON-1 and fibulin have antagonistic roles in control of organ shape.
abstract: 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.
authors.affiliation: Department of Genetics, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hesselson
authors.forename: Craig
authors.initials: C
authors.lastname: Newman
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Judith
authors.initials: J
authors.lastname: Kimble
mesh_terms: D051722:ADAM Proteins; D000071121:ADAMTS4 Protein; D000071119:ADAMTS9 Protein; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000196:embryology* / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D011348:Procollagen N-Endopeptidase; D034622:RNA Interference
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C060820:fibulin; D051722:ADAM Proteins; D000071119:ADAMTS9 Protein; C412869:ADAMTS9 protein, human; C119674:GON-1 protein, C elegans; D008666:Metalloendopeptidases; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human