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

Jingtong Gao, Lourdes Estrada, Soochin Cho, Ronald E. Ellis, Jerome L. Gorski

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)3049-3062
Number of pages14
JournalHuman Molecular Genetics
Volume10
Issue number26
StatePublished - Dec 15 2001
Externally publishedYes

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Guanine Nucleotide Exchange Factors
Caenorhabditis elegans
Morphogenesis
Genes
Dilatation
Rho Guanine Nucleotide Exchange Factors
rho GTP-Binding Proteins
Mutation
Sequence Analysis
Aarskog Syndrome
Alleles
Phenotype

All Science Journal Classification (ASJC) codes

  • Genetics

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Tha Caenorhabditis elegans homolog of FGD1, the human Cdc42 GEF gene responsible for faciogenital dysplasia, is critical for excretory cell morphogenesis. / Gao, Jingtong; Estrada, Lourdes; Cho, Soochin; Ellis, Ronald E.; Gorski, Jerome L.

In: Human Molecular Genetics, Vol. 10, No. 26, 15.12.2001, p. 3049-3062.

Research output: Contribution to journalArticle

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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.",
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