Involvement of fatty acid pathways and cortical interaction of the pronuclear complex in Caenorhabditis elegans embryonic polarity.
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.
Rappleye
Chad A
CA
Section of Cell and Developmental Biology, Univ, of California, San Diego, La Jolla, CA 92093, USA. rappleye@borcim.wustl.edu
Tagawa
Akiko
A
Le Bot
Nathalie
N
Ahringer
Julie
J
Aroian
Raffi V
RV
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
D005227:Fatty Acids; D009251:NADPH-Ferrihemoprotein Reductase; D000103:Acetyl-CoA Carboxylase