GON-1 and fibulin have antagonistic roles in control of organ shape.
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.
Hesselson
Daniel
D
Department of Genetics, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Newman
Craig
C
Kim
Kyung Won
KW
Kimble
Judith
J
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
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