Multiple Wnts Redundantly Control Polarity Orientation in Caenorhabditis elegans Epithelial Stem Cells

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

The effect of growth conditions on the seed size/number trade-off

BACKGROUND: If the amount of resources allocated to reproduction (K) is fixed, then an increase in seed mass (S) can only be achieved by a decrease in seed number (n = K/S). Thus, log(n) = log(K)-log(S) producing a slope of -1 when seed mass and number are plotted on log-log axes. However, in comparative studies, empirical support for a slope of -1 is limited and contentious, leading some to question the utility of this concept. METHODOLOGY/PRINCIPAL FINDINGS: First, we show that the expected slope depends on whether genotypes and species producing seeds of different mass are expected to reach the same adult size and that this in turn depends partly on the nature of growth. Second, we present experimental results using a population of recombinant inbred lines (RILs) of Arabidopsis thaliana. When these RILs are grown in large pots with plentiful nutrients, they exhibit a trade-off between seed size and number with a slope of -1.68 (+/-0.18) on log-log axes. This occurs because of genetic correlations between seed mass and adult size so that, under the right growth conditions, lines producing lighter seeds have the genetic potential to produce larger rosettes and hence a greater total mass of seeds. We re-grew lines in small pots (10 and 40 mm diameter) in a nutrient-poor substrate so that final adult size was heavily restricted by pot size. CONCLUSIONS/SIGNIFICANCE: Under our growth conditions, small-seeded lines were unable to produce a greater total mass of seeds. Hence a trade-off emerged between seed mass and seed number with a slope of -1.166+/-0.319 on log-log axes in 40-mm diameter pots (close to the expected value of -1), although the slope was 0.132+/-0.263 in 10-mm diameter pots, demonstrating that the nature of the trade-off is sensitive to the growth conditions

A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion

Wnt proteins are lipid-modified glycoproteins that play a central role in development, adult tissue homeostasis and disease. Secretion of Wnt proteins is mediated by the Wnt-binding protein Wntless (Wls), which transports Wnt from the Golgi network to the cell surface for release. It has recently been shown that recycling of Wls through a retromer-dependent endosome-to-Golgi trafficking pathway is required for efficient Wnt secretion, but the mechanism of this retrograde transport pathway is poorly understood. Here, we report that Wls recycling is mediated through a retromer pathway that is independent of the retromer sorting nexins SNX1-SNX2 and SNX5-SNX6. We have found that the unrelated sorting nexin, SNX3, has an evolutionarily conserved function in Wls recycling and Wnt secretion and show that SNX3 interacts directly with the cargo-selective subcomplex of the retromer to sort Wls into a morphologically distinct retrieval pathway. These results demonstrate that SNX3 is part of an alternative retromer pathway that functionally separates the retrograde transport of Wls from other retromer cargo