title: The Caenorhabditis elegans homolog of FGD1, the human Cdc42 GEF gene responsible for faciogenital dysplasia, is critical for excretory cell morphogenesis.
abstract: 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.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.forename: L
authors.initials: L
authors.lastname: Estrada
authors.forename: S
authors.initials: S
authors.lastname: Cho
authors.forename: R E
authors.initials: RE
authors.lastname: Ellis
authors.forename: J L
authors.initials: JL
authors.lastname: Gorski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D015536:Down-Regulation; D005147:Facial Bones / Q000002:abnormalities; D020662:Guanine Nucleotide Exchange Factors; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000196:embryology; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D009154:Mutation; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D017385:Sequence Homology; D013577:Syndrome; D014564:Urogenital Abnormalities / Q000235:genetics; D020764:cdc42 GTP-Binding Protein / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; C490796:FGD1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D015801:Helminth Proteins; D011506:Proteins; C434210:exc-5 protein, C elegans; D020764:cdc42 GTP-Binding Protein