title: A germ cell determinant reveals parallel pathways for germ line development in Caenorhabditis elegans.
abstract: Despite the central importance of germ cells for transmission of genetic material, our understanding of the molecular programs that control primordial germ cell (PGC) specification and differentiation are limited. Here, we present findings that X chromosome NonDisjunction factor-1 (XND-1), known for its role in regulating meiotic crossover formation, is an early determinant of germ cell fates in Caenorhabditis elegans. xnd-1 mutant embryos display a novel 'one PGC' phenotype as a result of G2 cell cycle arrest of the P4 blastomere. Larvae and adults display smaller germ lines and reduced brood size consistent with a role for XND-1 in germ cell proliferation. Maternal XND-1 proteins are found in the P4 lineage and are exclusively localized to the nucleus in PGCs, Z2 and Z3. Zygotic XND-1 turns on shortly thereafter, at the ∼300-cell stage, making XND-1 the earliest zygotically expressed gene in worm PGCs. Strikingly, a subset of xnd-1 mutants lack germ cells, a phenotype shared with nos-2, a member of the conserved Nanos family of germline determinants. We generated a nos-2 null allele and show that nos-2; xnd-1 double mutants display synthetic sterility. Further removal of nos-1 leads to almost complete sterility, with the vast majority of animals without germ cells. Sterility in xnd-1 mutants is correlated with an increase in transcriptional activation-associated histone modification and aberrant expression of somatic transgenes. Together, these data strongly suggest that xnd-1 defines a new branch for PGC development that functions redundantly with nos-2 and nos-1 to promote germline fates by maintaining transcriptional quiescence and regulating germ cell proliferation.
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Rana
authors.initials: R
authors.lastname: Mainpal
authors.affiliation: Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, NY 10016, USA Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nance
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA yanowitzjl@mwri.magee.edu.
authors.forename: Judith L
authors.initials: JL
authors.lastname: Yanowitz
mesh_terms: D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002843:Chromatin / Q000235:genetics* / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D016195:G2 Phase; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D005854:Germ Cells / Q000166:cytology*; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference; D013696:Temperature; D015533:Transcriptional Activation
chemical_list: D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; C400702:nos-1 protein, C elegans; C400703:nos-2 protein, C elegans; C553799:xnd-1 protein, C elegans
keywords: C. elegans; Germ line; Nanos; Primordial germ cells; Proliferation; XND-1