Multiple Wnts redundantly control polarity orientation in Caenorhabditis elegans epithelial stem cells

PLoS Genet. 2011 Oct;7(10):e1002308. doi: 10.1371/journal.pgen.1002308. Epub 2011 Oct 13.

Abstract

During development, cell polarization is often coordinated to harmonize tissue patterning and morphogenesis. However, how extrinsic signals synchronize cell polarization is not understood. In Caenorhabditis elegans, most mitotic cells are polarized along the anterior-posterior axis and divide asymmetrically. Although this process is regulated by a Wnt-signaling pathway, Wnts functioning in cell polarity have been demonstrated in only a few cells. We analyzed how Wnts control cell polarity, using compound Wnt mutants, including animals with mutations in all five Wnt genes. We found that somatic gonadal precursor cells (SGPs) are properly polarized and oriented in quintuple Wnt mutants, suggesting Wnts are dispensable for the SGPs' polarity, which instead requires signals from the germ cells. Thus, signals from the germ cells organize the C. elegans somatic gonad. In contrast, in compound but not single Wnt mutants, most of the six seam cells, V1-V6 (which are epithelial stem cells), retain their polarization, but their polar orientation becomes random, indicating that it is redundantly regulated by multiple Wnt genes. In contrast, in animals in which the functions of three Wnt receptors (LIN-17, MOM-5, and CAM-1) are disrupted--the stem cells are not polarized and divide symmetrically--suggesting that the Wnt receptors are essential for generating polarity and that they function even in the absence of Wnts. All the seam cells except V5 were polarized properly by a single Wnt gene expressed at the cell's anterior or posterior. The ectopic expression of posteriorly expressed Wnts in an anterior region and vice versa rescued polarity defects in compound Wnt mutants, raising two possibilities: one, Wnts permissively control the orientation of polarity; or two, Wnt functions are instructive, but which orientation they specify is determined by the cells that express them. Our results provide a paradigm for understanding how cell polarity is coordinated by extrinsic signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Polarity / genetics*
  • Cell Polarity / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology*
  • Gene Expression Regulation, Developmental
  • Germ Cells / physiology
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Gonads / cytology
  • Gonads / metabolism
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism
  • Morphogenesis
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Receptors, Wnt / genetics
  • Receptors, Wnt / metabolism
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway / genetics

Substances

  • CWN-1 protein, C elegans
  • CWN-2 protein, C elegans
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Egl-20 protein, C elegans
  • Glycoproteins
  • High Mobility Group Proteins
  • LIN-44 protein, C elegans
  • Mutant Proteins
  • Receptors, Wnt
  • Wnt Proteins
  • pop-1 protein, C elegans