The Caenorhabditis elegans homolog of FGD1, the human Cdc42 GEF gene responsible for faciogenital dysplasia, is critical for excretory cell morphogenesis

Hum Mol Genet. 2001 Dec 15;10(26):3049-62. doi: 10.1093/hmg/10.26.3049.


FGD1 mutations result in faciogenital dysplasia, an X-linked human disease that affects skeletogenesis. FGD1 encodes a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase Cdc42. To gain insight into the function of FGD1, we have isolated and characterized fgd-1, the Caenorhabditis elegans homolog of the human FGD1 gene. Comparative sequence analyses show that fgd-1 and FGD1 share a similar structural organization and a high degree of sequence identity throughout shared signaling domains. In nematodes, interference with fgd-1 expression results in excretory cell abnormalities and cystic dilation of the excretory cell canals. Molecular lesions associated with two exc-5 alleles affect the fgd-1 gene, and fgd-1 transgenic expression rescues the Exc-5 phenotype. Together, these data confirm that the fgd-1 transcript corresponds to the exc-5 gene. Transgenic expression studies show that fgd-1 has a limited pattern of expression that is confined to the excretory cell during development, a finding that suggests that the C.elegans FGD-1 protein might function in a cell autonomous manner. Serial observations indicate that fgd-1 mutations lead to developmental excretory cell abnormalities that cause cystic dilation and interfere with canal process extension. Based on these data, we conclude that fgd-1 is the C.elegans homolog of the human FGD1 gene, a new member of the FGD1-related family of RhoGEF genes, and that fgd-1 plays a critical role in excretory cell morphogenesis and cellular organization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins*
  • Down-Regulation
  • Facial Bones / abnormalities
  • Guanine Nucleotide Exchange Factors
  • Helminth Proteins / genetics
  • Helminth Proteins / physiology*
  • Humans
  • Kidney / embryology
  • Molecular Sequence Data
  • Morphogenesis / genetics
  • Morphogenesis / physiology
  • Mutation
  • Polymerase Chain Reaction
  • Proteins / genetics
  • Sequence Homology
  • Syndrome
  • Urogenital Abnormalities / genetics
  • cdc42 GTP-Binding Protein / genetics


  • Caenorhabditis elegans Proteins
  • FGD1 protein, human
  • Guanine Nucleotide Exchange Factors
  • Helminth Proteins
  • Proteins
  • exc-5 protein, C elegans
  • cdc42 GTP-Binding Protein