title: Involvement of fatty acid pathways and cortical interaction of the pronuclear complex in Caenorhabditis elegans embryonic polarity.
abstract: BACKGROUND
  Cell polarity is essential for many decisions made during development. While investigation of polarity-specific factors has yielded great insights into the polarization process, little is known on how these polarity-specific factors link to the basic cellular mechanisms that function in non-polarity aspects of the cell. To better understand the mechanisms that establish embryonic polarity, we investigated genes required for polarity in the one-cell C. elegans embryo that are also required for other non-polarity functions. This has led to the identification of the Pod-class of mutants that are characterized by osmosensitive embryos and defects in anterior-posterior polarity.
  
  
  RESULTS
  Mutation in either of two loci of this class, emb-8 and pod-2, disrupts embryonic polarization and results in osmotically-sensitive embryos. Loss of emb-8, a previously uncharacterized polarity gene, causes mislocalization of PAR-3 and PAR-2 that molecularly mark the anterior and posterior cortices. emb-8 encodes NADPH-cytochrome P450 reductase, a protein supplying electrons to cytochrome P450-family enzymes, some of which catalyze fatty acid modifications. Cloning of the previously characterized polarity gene pod-2 reveals it encodes acetyl-CoA carboxylase, an enzyme that catalyzes the first step in de novo fatty acid synthesis. Depletion of fatty acid synthase, the next enzyme in the biosynthetic pathway, by RNA-interference (RNAi) also causes similar loss of one-cell polarity. Furthermore, pod-2 polarity defects can be rescued by addition of exogenous fatty acids. By following the behavior of the pronucleus in emb-8 and pod-2 mutant embryos, we demonstrate that loss of polarity correlates with impaired interaction between the pronucleus-centrosome complex and the posterior cortex.
  
  
  CONCLUSIONS
  The characterization of emb-8 and pod-2 mutant embryos suggests that the pronucleus-centrosome complex interaction with the cortex plays a direct role in establishing polarity and that fatty acid pathways are important for this polarizing event.
authors.affiliation: Section of Cell and Developmental Biology, Univ, of California, San Diego, La Jolla, CA 92093, USA. rappleye@borcim.wustl.edu
authors.forename: Chad A
authors.initials: CA
authors.lastname: Rappleye
authors.forename: Akiko
authors.initials: A
authors.lastname: Tagawa
authors.forename: Nathalie
authors.initials: N
authors.lastname: Le Bot
authors.forename: Julie
authors.initials: J
authors.lastname: Ahringer
authors.forename: Raffi V
authors.initials: RV
authors.lastname: Aroian
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000502:physiology; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D016764:Cell Polarity / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D017238:Genes, Helminth / Q000502:physiology; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000502:physiology; D009997:Osmotic Pressure
chemical_list: D005227:Fatty Acids; D009251:NADPH-Ferrihemoprotein Reductase; D000103:Acetyl-CoA Carboxylase