Genetic and molecular analysis of fox-1, a numerator element involved in Caenorhabditis elegans primary sex determination.

fox-1 was previously identified as a candidate numerator element based on its overexpression phenotype. FOX-1 is an RRM-type RNA-binding protein, which can bind RNAs in vitro. Western analysis detects FOX-1 throughout development. fox-1::lacZ comes on ubiquitously early during embryogenesis. Postembryonically, fox-1::lacZ is expressed sex specifically in a subset of cells in the head and tail. We describe a Tc1-derived deletion allele [fox-1(Delta)] that removes the RRM domain. fox-1(Delta) confers no phenotype in XXs, but can rescue XO-specific lethality and feminization caused by duplications of the left end of the X. fox-1(Delta) synergizes with putative numerators, resulting in abnormal XX development. Genetic analysis indicated that fox-1(Delta) leads to a slight increase in xol-1 activity, while fox-1(gf) leads to partial loss of xol-1 activity, and xol-1 is epistatic to fox-1. RNase protection experiments revealed increased levels of the 2.2-kb xol-1 message in fox-1(Delta) animals, and reduced levels in fox-1(gf) animals. Additionally, fox-1(Delta) impairs male mating efficiency, which, we propose, represents another function of fox-1, independent of xol-1 and its role in sex determination.

[1]  M. Frohman,et al.  Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[2]  T. Cline Evidence that sisterless-a and sisterless-b are two of several discrete "numerator elements" of the X/A sex determination signal in Drosophila that switch Sxl between two alternative stable expression states. , 1988, Genetics.

[3]  J. Hodgkin Genetic sex determination mechanisms and evolution. , 1992, BioEssays : news and reviews in molecular, cellular and developmental biology.

[4]  E. Harlow,et al.  Antibodies: A Laboratory Manual , 1988 .

[5]  J. Hodgkin,et al.  Molecular analysis of the C. elegans sex-determining gene tra-1: A gene encoding two zinc finger proteins , 1992, Cell.

[6]  B. Meyer Sex Determination and X Chromosome Dosage Compensation , 1997 .

[7]  W. Wood The Nematode Caenorhabditis elegans , 1988 .

[8]  C. Huynh,et al.  A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites. , 1992, Genetics.

[9]  R. Plasterk,et al.  Target-selected gene inactivation in Caenorhabditis elegans by using a frozen transposon insertion mutant bank. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[10]  C M Loer,et al.  Serotonin-deficient mutants and male mating behavior in the nematode Caenorhabditis elegans , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  R. Pulak,et al.  mRNA surveillance by the Caenorhabditis elegans smg genes. , 1993, Genes & development.

[12]  B. Meyer,et al.  X chromosome dosage compensation and its relationship to sex determination in C. elegans , 1993 .

[13]  S. Brenner,et al.  Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans. , 1977, Genetics.

[14]  M. de Bono,et al.  Evolution of sex determination in caenorhabditis: unusually high divergence of tra-1 and its functional consequences. , 1996, Genetics.

[15]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[16]  B. Meyer,et al.  X-chromosome-counting mechanisms that determine nematode sex , 1997, Nature.

[17]  R. Sikorski,et al.  A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. , 1989, Genetics.

[18]  B. Bainbridge,et al.  Genetics , 1981, Experientia.

[19]  B. Meyer,et al.  Identification of X chromosome regions in Caenorhabditis elegans that contain sex-determination signal elements. , 1994, Genetics.

[20]  S. Parkhurst,et al.  Sex determination and dosage compensation: lessons from flies and worms. , 1994, Science.

[21]  P. Goodfellow,et al.  Rapid sequence evolution of the mammalian sex-determining gene SRY , 1993, Nature.

[22]  S. Ho,et al.  Site-directed mutagenesis by overlap extension using the polymerase chain reaction. , 1989, Gene.

[23]  B. Meyer,et al.  xol-1: A gene that controls the male modes of both sex determination and X chromosome dosage compensation in C. elegans , 1988, Cell.

[24]  A. Fire Integrative transformation of Caenorhabditis elegans , 1986, The EMBO journal.

[25]  G. Dreyfuss,et al.  RNA binding specificity of hnRNP proteins: a subset bind to the 3′ end of introns. , 1988, The EMBO journal.

[26]  B. Meyer,et al.  Vive la différence: males vs females in flies vs worms. , 1996, Annual review of genetics.

[27]  N. Rhind,et al.  xo1-1 acts as an early switch in the C. elegans male/hermaphrodite decision , 1995, Cell.

[28]  A. Zorn,et al.  The KH domain protein encoded by quaking functions as a dimer and is essential for notochord development in Xenopus embryos. , 1997, Genes & development.

[29]  R. Plasterk Reverse genetics of Caenorhabditis elegans. , 1992, BioEssays : news and reviews in molecular, cellular and developmental biology.

[30]  J. Fleming,et al.  Basic culture methods. , 1995, Methods in cell biology.

[31]  D. Albertson,et al.  Identification of a candidate primary sex determination locus, fox-1, on the X chromosome of Caenorhabditis elegans. , 1994, Development.

[32]  H. Horvitz,et al.  A novel dominant transformer allele of the sex-determining gene her-1 of Caenorhabditis elegans. , 1988, Genetics.

[33]  S. Brenner,et al.  Nondisjunction Mutants of the Nematode CAENORHABDITIS ELEGANS. , 1979, Genetics.

[34]  J. Hodgkin,et al.  Natural variation and copulatory plug formation in Caenorhabditis elegans. , 1997, Genetics.

[35]  R. K. Herman,et al.  Polyploids and sex determination in Caenorhabditis elegans. , 1979, Genetics.

[36]  P. Kuwabara A novel regulatory mutation in the C. elegans sex determination gene tra-2 defines a candidate ligand/receptor interaction site. , 1996, Development.