Motegi F et al. (2006) Tanpakushitsu Kakusan Koso "[Cell polarization: lessons from C. elegans asymmetric cell division]"

Motegi F, Sugimoto A

[Tanpakushitsu Kakusan Koso, 2006]

Motegi F et al. (2007) J Cell Biol "Revisiting the role of microtubules in C. elegans polarity."

Motegi F, Seydoux G

[J Cell Biol, 2007]

Cells must break symmetry to acquire polarity. Microtubules have been implicated in the induction of asymmetry in several cell types, but their role in the Caenorhabditis elegans zygote, a classic polarity model, has remained uncertain. One study (see Tsai and Ahringer on p. 397 of this issue) brings new light to this problem by demonstrating that severe loss of microtubules impairs polarity onset in C. elegans.

Motegi F et al. (2006) Nat Cell Biol "Sequential functioning of the ECT-2 RhoGEF, RHO-1 and CDC-42 establishes cell polarity in Caenorhabditis elegans embryos."

Sugimoto A, Motegi F

[Nat Cell Biol, 2006]

During development, the establishment of cell polarity is important for cells to undergo asymmetric cell divisions that give rise to diverse cell types. In C. elegans embryos, cues from the centrosome trigger the cortical flow of an actomyosin network, leading to the formation of anterior-posterior polarity. However, its precise mechanism is poorly understood. Here, we show that small GTPases have sequential and crucial functions in this process. ECT-2, a potential guanine nucleotide-exchange factor (GEF) for RHO-1, was uniformly distributed at the cortex before polarization, but was excluded from the posterior cortex by the polarity cue from the centrosomes. This local exclusion of ECT-2 led to an asymmetric RHO-1 distribution, which generated a cortical flow of the actomyosin that translocated PAR proteins and CDC-42 (Refs 4, 5) to the anterior cortex. Polarized CDC-42 was, in turn, involved in maintaining the established anterior-cortical domains. Our results suggest that a local change in the function of ECT-2 and RHO-1 links the centrosomal polarity cue with the polarization of the cell cortex.

Motegi F et al. (2006) Dev Cell "Two phases of astral microtubule activity during cytokinesis in C. elegans embryos."

Velarde NV, Sugimoto A, Motegi F, Piano F

[Dev Cell, 2006]

Microtubules of the mitotic spindle are believed to provide positional cues for the assembly of the actin-based contractile ring and the formation of the subsequent cleavage furrow during cytokinesis. In Caenorhabditis elegans, astral microtubules have been thought to inhibit cortical contraction outside the cleavage furrow. Here, we demonstrate by live imaging and RNA interference (RNAi) that astral microtubules play two distinct roles in initiating cleavage furrow formation. In early anaphase, microtubules are required for contractile ring assembly; in late anaphase, microtubules show different cortical behavior and seem to suppress cortical contraction at the poles, as suggested in previous studies. These two distinct phases of microtubule behavior depend on distinct regulatory pathways, one involving the gamma-tubulin complex and the other requiring aurora-A kinase. We propose that temporal and spatial regulation of two distinct phases of astral microtubule behavior is crucial in specifying the position and timing of furrowing.

Motegi F et al. (2019) Curr Opin Cell Biol "Novel approaches to link apicobasal polarity to cell fate specification."

Plachta N, Viasnoff V, Motegi F

[Curr Opin Cell Biol, 2019]

Understanding the development of apicobasal polarity (ABP) is a long-standing problem in biology. The molecular components involved in the development and maintenance of APB have been largely identified and are known to have ubiquitous roles across organisms. Our knowledge of the functional consequences of ABP establishment and maintenance is far less comprehensive. Recent studies using novel experimental approaches and cellular models have revealed a growing link between ABP and the genetic program of cell lineage. This mini-review describes some of the most recent advances in this new field, highlighting examples from Caenorhabditis elegans and mouse embryos, human pluripotent stem cells, and epithelial cells. We also speculate on the most interesting and challenging avenues that can be explored.

Motegi F et al. (2013) Philos Trans R Soc Lond B Biol Sci "The PAR network: redundancy and robustness in a symmetry-breaking system."

Motegi F, Seydoux G

[Philos Trans R Soc Lond B Biol Sci, 2013]

To become polarized, cells must first 'break symmetry'. Symmetry breaking is the process by which an unpolarized, symmetric cell develops a singularity, often at the cell periphery, that is used to develop a polarity axis. The Caenorhabditis elegans zygote breaks symmetry under the influence of the sperm-donated centrosome, which causes the PAR polarity regulators to sort into distinct anterior and posterior cortical domains. Modelling analyses have shown that cortical flows induced by the centrosome combined with antagonism between anterior and posterior PARs (mutual exclusion) are sufficient, in principle, to break symmetry, provided that anterior and posterior PAR activities are precisely balanced. Experimental evidence indicates, however, that the system is surprisingly robust to changes in cortical flows, mutual exclusion and PAR balance. We suggest that this robustness derives from redundant symmetry-breaking inputs that engage two positive feedback loops mediated by the anterior and posterior PAR proteins. In particular, the PAR-2 feedback loop stabilizes the polarized state by creating a domain where posterior PARs are immune to exclusion by anterior PARs. The two feedback loops in the PAR network share characteristics with the two feedback loops in the Cdc42 polarization network of Saccharomyces cerevisiae.

Motegi F et al. (2011) Nat Cell Biol "Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans zygotes."

Seydoux G, Hao Y, Griffin E, Cuenca AA, Zonies S, Motegi F

[Nat Cell Biol, 2011]

A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance, but the mechanisms that initiate the formation of asymmetric PAR domains are not understood. Here, we describe one pathway used by the sperm-donated centrosome to polarize the PAR proteins in Caenorhabditis elegans zygotes. Before polarization, cortical aPKC excludes PAR-1 kinase and its binding partner PAR-2 by phosphorylation. During symmetry breaking, microtubules nucleated by the centrosome locally protect PAR-2 from phosphorylation by aPKC, allowing PAR-2 and PAR-1 to access the cortex nearest the centrosome. Cortical PAR-1 phosphorylates PAR-3, causing the PAR-3-aPKC complex to leave the cortex. Our findings illustrate how microtubules, independently of actin dynamics, stimulate the self-organization of PAR proteins by providing local protection against a global barrier imposed by aPKC.

Yamamoto K et al. (2023) Curr Biol "Cell polarity: Adapting the PAR cascade to diverse cellular contexts."

Motegi F, Yamamoto K

[Curr Biol, 2023]

Two new studies shed light on the intricacies of Caenorhabditis elegans embryo patterning, revealing how the conserved interaction and crosstalk of PAR proteins are adapted to perceive distinct cues, ultimately shaping unique asymmetries in form and function.

Gan WJ et al. (2020) Front Cell Dev Biol "Mechanochemical Control of Symmetry Breaking in the Caenorhabditis elegans Zygote."

Gan WJ, Motegi F

[Front Cell Dev Biol, 2020]

Cell polarity is the asymmetric organization of cellular components along defined axes. A key requirement for polarization is the ability of the cell to break symmetry and achieve a spatially biased organization. Despite different triggering cues in various systems, symmetry breaking (SB) usually relies on mechanochemical modulation of the actin cytoskeleton, which allows for advected movement and reorganization of cellular components. Here, the mechanisms underlying SB in <i>Caenorhabditis elegans</i> zygote, one of the most popular models to study cell polarity, are reviewed. A zygote initiates SB through the centrosome, which modulates mechanics of the cell cortex to establish advective flow of cortical proteins including the actin cytoskeleton and partitioning defective (PAR) proteins. The chemical signaling underlying centrosomal control of the Aurora A kinase-mediated cascade to convert the organization of the contractile actomyosin network from an apolar to polar state is also discussed.

Bastock R et al. (2011) Dev Cell "Going with the flow: an elegant model for symmetry breaking."

Bastock R, St Johnston D

[Dev Cell, 2011]

The entry of the sperm centrosome polarizes the anterior-posterior axis of the C. elegans zygote by inducing the formation of complementary cortical Par protein domains. Recent papers from the Seydoux and Grill laboratories (Goehring et al., 2011b and Motegi et al., 2011) reveal how two different symmetry-breaking mechanisms produce the same final pattern through interactions between Par proteins.