Acto-myosin reorganization and PAR polarity in<i>C. elegans</i>

Cowan, Carrie; Hyman, Anthony A.

doi:10.1242/dev.000513

Cited by 110 publications

(114 citation statements)

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“…RNAi depletions that cause early cell cycle arrest or altered cell division patterns and eventually embryonic lethality may lead to a diffuse or ''missegregated'' P-granule pattern. In fact, P granules have been used as a marker to study cell polarity for .20 years, and some examples of P-granule missegregation have been intensively studied (e.g., Gonczy and Rose 2005;Cowan and Hyman 2007). In our secondary and tertiary screens, we more closely examined whether a defective GFPTPGL-1 phenotype appeared to be correlated with abnormal nuclear morphology, embryo patterning defects, and/or early arrest (Table 1).…”

Section: Resultsmentioning

confidence: 99%

A Genomewide RNAi Screen for Genes That Affect the Stability, Distribution and Function of P Granules in Caenorhabditis elegans

2009

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P granules are non-membrane-bound organelles found in the germ-line cytoplasm throughout Caenorhabditis elegans development. Like their ''germ granule'' counterparts in other animals, P granules are thought to act as determinants of the identity and special properties of germ cells, properties that include the unique ability to give rise to all tissues of future generations of an organism. Therefore, understanding how P granules work is critical to understanding how cellular immortality and totipotency are retained, gained, and lost. Here we report on a genomewide RNAi screen in C. elegans, which identified 173 genes that affect the stability, localization, and function of P granules. Many of these genes fall into specific classes with shared P-granule phenotypes, allowing us to better understand how cellular processes such as protein degradation, translation, splicing, nuclear transport, and mRNA homeostasis converge on P-granule assembly and function. One of the more striking phenotypes is caused by the depletion of CSR-1, an Argonaute associated with an endogenous siRNA pathway that functions in the germ line. We show that CSR-1 and two other endo-siRNA pathway members, the RNA-dependent RNA polymerase EGO-1 and the helicase DRH-3, act to antagonize RNA and P-granule accumulation in the germ line. Our findings strengthen the emerging view that germ granules are involved in numerous aspects of RNA metabolism, including an endo-siRNA pathway in germ cells.

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Section: Resultsmentioning

confidence: 99%

A Genomewide RNAi Screen for Genes That Affect the Stability, Distribution and Function of P Granules in Caenorhabditis elegans

2009

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“…The current model for polarity establishment in C. elegans embryos proposes that the activity of the acto-myosin cortex regulates the distribution of the PAR proteins (1). In this model the cortex is an isotropically contractile meshwork before symmetry breaking.…”

Section: Discussionmentioning

confidence: 99%

“…The formation of cortical domains involves two interlinked problems: How does a cell initially set the size of its domains, and how is the size of the domains maintained during asymmetric functioning? Recent work in a number of organisms has identified many of the components of these cortical domains (1)(2)(3)(4). However, it remains unclear how these components determine the size of the domains.…”

mentioning

confidence: 99%

The Rho GTPase-activating proteins RGA-3 and RGA-4 are required to set the initial size of PAR domains in Caenorhabditis elegans one-cell embryos

Schonegg

Constantinescu

Hoege

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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115

129

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Caenorhabditis elegans embryos establish cortical domains of PAR proteins of reproducible size before asymmetric cell division. The ways in which the size of these domains is set remain unknown. Here we identify the GTPase-activating proteins (GAPs) RGA-3 and RGA-4, which regulate the activity of the small GTPase RHO-1. rga-3/4(RNAi) embryos have a hypercontractile cortex, and the initial relative size of their anterior and posterior PAR domains is altered. Thus, RHO-1 activity appears to control the level of cortical contractility and concomitantly the size of cortical domains. These data support the idea that in C. elegans embryos the initial size of the PAR domains is set by regulating the contractile activity of the acto-myosin cytoskeleton through the activity of RHO-1. RGA-3/4 have functions different from CYK-4, the other known GAP required for the first cell division, showing that different GAPs cooperate to control the activity of the acto-myosin cytoskeleton in the first cell division of C. elegans embryos.cell polarity ͉ cortex ͉ NMY-2 ͉ contractility C ell polarization allows a spatial differentiation of cellular functions. For instance, cells polarize to migrate toward a signal, to secrete molecules in a biased direction, and to divide asymmetrically to generate different daughter cells. Polarity establishment depends on the segregation of the cell cortex into different cortical domains, which then dictate asymmetric functions within the cytoplasm. The formation of cortical domains involves two interlinked problems: How does a cell initially set the size of its domains, and how is the size of the domains maintained during asymmetric functioning? Recent work in a number of organisms has identified many of the components of these cortical domains (1-4). However, it remains unclear how these components determine the size of the domains. How can the collective activity of molecules determine the size of a domain that might be several orders of magnitude larger than the molecules themselves?The formation of polarity in Caenorhabditis elegans embryos is an excellent system to study the establishment of cortical domains. The polarization of the cortex is marked by the formation of PAR protein domains: An anterior domain comprising PAR-3, PAR-6, and atypical PKC (PKC-3), together with the Rho GTPase CDC-42; and a posterior domain comprising PAR-1 and PAR-2. After meiosis, the members of the anterior PAR complex are localized all over the cortex. When symmetry is broken by the centrosome, the anterior complex retracts toward the anterior of the embryo. Concomitantly, the posterior PAR complex fills in the cortical area left by the retraction of the anterior PAR complex, thereby establishing the polarity of a one-cell embryo (5, 6). During the subsequent maintenance phase, the two PAR domains have consistent sizes {a variation of Ϸ2% between embryos [unpublished data and supporting information (SI) Text]} until cytokinesis. These cortical domains control the asymmetric localization of cell fate determinants a...

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“…Although the actomyosin cortex has been described as a contractile superficial gel over 70 years ago [256], we have only very recently begun to understand how global aspects of cell behavior are triggered by cortical flow, namely by a gradient in actomyosin contractility to drive flow and a sufficiently large viscosity of the cortex to allow flow to be long-ranged [13]. Patterning of all three major body axes, which are established in first three consecutive divisions of embryogenesis, relies on cortical actomyosin activity in C. elegans [5,7,8,25,26]. The inductive cue that established polarity in this system is sperm entry which triggers anteriorly directed flows in actomyosin cortex in the 1-cell C. elegans embryo through the RhoGAP CYK-4 [14,15,255,[257][258][259][260][261].…”

Section: Actomyosinmentioning

confidence: 99%

“…Independently of the specific developmental process, metazoa seem to use a remarkably conserved molecular toolset for cue-dependent symmetry breaking including actomyosin and microtubule networks, the PAR genes, Wnt and Notch signaling [7][8][9][10]; differential deployment and the vast number of accessory factors ensure that this toolset can generate drastically different species-specific outcomes on a macroscopic scale. Table 1.…”

Section: Introductionmentioning

confidence: 99%

Cytoskeletal Symmetry Breaking and Chirality: From Reconstituted Systems to Animal Development

Pohl

2015

Symmetry

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Animal development relies on repeated symmetry breaking, e.g., during axial specification, gastrulation, nervous system lateralization, lumen formation, or organ coiling. It is crucial that asymmetry increases during these processes, since this will generate higher morphological and functional specialization. On one hand, cue-dependent symmetry breaking is used during these processes which is the consequence of developmental signaling. On the other hand, cells isolated from developing animals also undergo symmetry breaking in the absence of signaling cues. These spontaneously arising asymmetries are not well understood. However, an ever growing body of evidence suggests that these asymmetries can originate from spontaneous symmetry breaking and self-organization of molecular assemblies into polarized entities on mesoscopic scales. Recent discoveries will be highlighted and it will be discussed how actomyosin and microtubule networks serve as common biomechanical systems with inherent abilities to drive spontaneous symmetry breaking.

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Acto-myosin reorganization and PAR polarity inC. elegans

Cited by 110 publications

References 76 publications

A Genomewide RNAi Screen for Genes That Affect the Stability, Distribution and Function of P Granules in Caenorhabditis elegans

A Genomewide RNAi Screen for Genes That Affect the Stability, Distribution and Function of P Granules in Caenorhabditis elegans

The Rho GTPase-activating proteins RGA-3 and RGA-4 are required to set the initial size of PAR domains in Caenorhabditis elegans one-cell embryos

Cytoskeletal Symmetry Breaking and Chirality: From Reconstituted Systems to Animal Development

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