MEX-5 asymmetry in one-cell<i>C. elegans</i>embryos requires PAR-4-and PAR-1-dependent phosphorylation

Tenlen, Jennifer R.; Molk, Jeffrey N.; London, Nitobe; Page, Barbara D.; Priess, James R

doi:10.1242/dev.027060

Cited by 73 publications

(153 citation statements)

References 56 publications

(79 reference statements)

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“…This ratio was reduced to 1.5 6 0.3 (n ¼ 35) in par-1(zu310) embryos, a value significantly different from wild type (P ¼ 10 À7 ) ( Figure 4M). Consistent with previously published data (Tenlen et al 2008), MEX-5 distribution in mpk-1(ga111) mutants did not differ significantly from wild-type animals ( Figure 4, C and M), even at a fully restrictive temperature for the allele ga111 ( Figure S5), but the MEX-5 fluorescence ratio measured in mpk-1; par-1 double mutant embryos (1.8 6 0.4; n ¼ 35) was significantly higher than in par-1 embryos (P ¼ 0.004) (Figure 4, B, D, and M). However, this fluorescence ratio was still significantly lower than the ratio measured in wild-type embryos (P ¼ 0.001).…”

Section: Resultssupporting

confidence: 93%

“…Disrupting mpk-1 function restores cell fate specification in par-1(zu310) mutants: PAR-1 is required for the segregation of a number of cell fate determinants along the anteroposterior axis of the one-cell embryo by regulating the anterior localization of MEX-5/6 (Schubert et al 2000;Cuenca et al 2003;Tenlen et al 2008). Consistent with this, we find that MEX-5 localizes to both daughter cells in par-1(zu310) embryos at semirestrictive temperature (Figure 4, A and B).…”

Section: Resultsmentioning

confidence: 99%

“…This suggests that in wildtype animals, PAR-1 acts in part by restricting MEX-5 and MEX-6 to the anterior of the embryo. The precise mechanism of this regulation is not known, but an elegant study performed for MEX-5 indicates that differential protein mobility in the anterior and posterior cytoplasm of the one-cell embryo contributes to this asymmetry (Tenlen et al 2008). While increased mobility in the posterior of the one-cell embryo correlates with a par-1-and par-4-dependent phosphorylation on MEX-5, the kinase directly phosphorylating MEX-5 remains to be identified (Tenlen et al 2008).…”

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confidence: 99%

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MAP Kinase Signaling Antagonizes PAR-1 Function During Polarization of the Early Caenorhabditis elegans Embryo

et al. 2009

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PAR proteins (partitioning defective) are major regulators of cell polarity and asymmetric cell division. One of the par genes, par-1, encodes a Ser/Thr kinase that is conserved from yeast to mammals. In Caenorhabditis elegans, par-1 governs asymmetric cell division by ensuring the polar distribution of cell fate determinants. However the precise mechanisms by which PAR-1 regulates asymmetric cell division in C. elegans remain to be elucidated. We performed a genomewide RNAi screen and identified six genes that specifically suppress the embryonic lethal phenotype associated with mutations in par-1. One of these suppressors is mpk-1, the C. elegans homolog of the conserved mitogen activated protein (MAP) kinase ERK. Loss of function of mpk-1 restored embryonic viability, asynchronous cell divisions, the asymmetric distribution of cell fate specification markers, and the distribution of PAR-1 protein in par-1 mutant embryos, indicating that this genetic interaction is functionally relevant for embryonic development. Furthermore, disrupting the function of other components of the MAPK signaling pathway resulted in suppression of par-1 embryonic lethality. Our data therefore indicates that MAP kinase signaling antagonizes PAR-1 signaling during early C. elegans embryonic polarization.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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MAP Kinase Signaling Antagonizes PAR-1 Function During Polarization of the Early Caenorhabditis elegans Embryo

et al. 2009

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“…The asymmetric localization of maternal proteins to restricted blastomeres, which is an essential step in asymmetric divisions and cell fate-specification in early C. elegans embryos, is achieved by various mechanisms, including asymmetric distribution, retention and/or degradation (Reese et al, 2000;Hao et al, 2006;Tenlen et al, 2008;Griffin et al, 2011). Maternal factors can also be deposited into the egg as mRNAs and asymmetrically translated in a subset of blastomeres.…”

Section: Introductionmentioning

confidence: 99%

Regulation of maternal Wnt mRNA translation inC. elegansembryos

et al. 2013

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The restricted spatiotemporal translation of maternal mRNAs, which is crucial for correct cell fate specification in early C. elegans embryos, is regulated primarily through the 3′UTR. Although genetic screens have identified many maternally expressed cell fatecontrolling RNA-binding proteins (RBPs), their in vivo targets and the mechanism(s) by which they regulate these targets are less clear. These RBPs are translated in oocytes and localize to one or a few blastomeres in a spatially and temporally dynamic fashion unique for each protein and each blastomere. Here, we characterize the translational regulation of maternally supplied mom-2 mRNA, which encodes a Wnt ligand essential for two separate cell-cell interactions in early embryos. A GFP reporter that includes only the mom-2 3′UTR is translationally repressed properly in oocytes and early embryos, and then correctly translated only in the known Wnt signaling cells. We show that the spatiotemporal translation pattern of this reporter is regulated combinatorially by a set of nine maternally supplied RBPs. These nine proteins all directly bind the mom-2 3′UTR in vitro and function as positive or negative regulators of mom-2 translation in vivo. The net translational readout for the mom-2 3′UTR reporter is determined by competitive binding between positive-and negativeacting RBPs for the 3′UTR, along with the distinct spatiotemporal localization patterns of these regulators. We propose that the 3′UTR of maternal mRNAs contains a combinatorial code that determines the topography of associated RBPs, integrating positive and negative translational inputs.

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“…Cytoplasmic gradients established in embryogenesis have conventionally been explained by hypothetical generation/degradation mechanisms (Crick, 1970;Gregor et al, 2007;Tostevin and Howard, 2008). However, recent reports suggest that multiple cytoplasmic proteins are enriched to opposite ends of the C. elegans zygote by related mechanisms in which generation and degradation do not play a role (Daniels et al, 2009;Tenlen et al, 2008). The germline determinant PIE-1 is enriched in the posterior cytoplasm, whereas the somatic cell-fate determinant MEX-5 is enriched in the anterior cytoplasm of the early embryo.…”

Section: Introductionmentioning

confidence: 99%

MEX-5 enrichment in the C. elegans early embryo mediated by differential diffusion

et al. 2010

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SUMMARYSpecification of germline and somatic cell lineages in C. elegans originates in the polarized single-cell zygote. Several cell-fate determinants are partitioned unequally along the anterior-posterior axis of the zygote, ensuring the daughter cells a unique inheritance upon asymmetric cell division. Recent studies have revealed that partitioning of the germline determinant PIE-1 and the somatic determinant MEX-5 involve protein redistribution accompanied by spatiotemporal changes in protein diffusion rates. Here, we characterize the dynamics of MEX-5 in the zygote and propose a novel reaction/diffusion model to explain both its anterior enrichment and its remarkable intracellular dynamics without requiring asymmetrically distributed binding sites. We propose that asymmetric cortically localized PAR proteins mediate the anterior enrichment of MEX-5 by reversibly changing its diffusion rate at spatially distinct points in the embryo, thus generating a stable concentration gradient along the anteriorposterior axis of the cell. This work extends the scope of reaction/diffusion models to include not only germline morphogens, but also somatic determinants.

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MEX-5 asymmetry in one-cellC. elegansembryos requires PAR-4-and PAR-1-dependent phosphorylation

Cited by 73 publications

References 56 publications

MAP Kinase Signaling Antagonizes PAR-1 Function During Polarization of the Early Caenorhabditis elegans Embryo

MAP Kinase Signaling Antagonizes PAR-1 Function During Polarization of the Early Caenorhabditis elegans Embryo

Regulation of maternal Wnt mRNA translation inC. elegansembryos

MEX-5 enrichment in the C. elegans early embryo mediated by differential diffusion

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