The<i>C. elegans</i>Myt1 ortholog is required for the proper timing of oocyte maturation

Burrows, Anna E.; Sceurman, Bonnielin K.; Kosinski, Mary; Richie, Christopher T.; Sadler, Penny L.; Schumacher, Jill M.; Golden, Andy

doi:10.1242/dev.02241

Cited by 75 publications

(136 citation statements)

References 65 publications

(67 reference statements)

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“…Intriguingly, we observed effects on the steadystate levels of T161-activating phosphorylation associated with the Cdk1(T14A)-VFP mutant ( Figure 1C) that were consistent with a proposed role for T14 phosphorylation in promoting or stabilizing T161-activating phosphorylation of Cdk1/Cyclin complexes during G2 phase (Coulonval et al 2011). Indeed, such a role for T14 phosphorylation of Cdk1 could explain requirements for Myt1 activity in cells that undergo prolonged developmentally regulated G2-phase arrest during Drosophila male meiosis or oocyte maturation in other systems (Karaiskou et al 2004;Jin et al 2005;Burrows et al 2006). Thus, dual phosphorylation of Cdk1 by Myt1 kinases may have evolved as a dynamic mechanism for facilitating developmentally regulated G2-phase checkpoint arrest without compromising the cell's ability to initiate mitosis without delay when triggered by Cdc25 dephosphorylation.…”

Section: Discussionsupporting

confidence: 75%

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Dual Phosphorylation of Cdk1 Coordinates Cell Proliferation with Key Developmental Processes in Drosophila

et al. 2014

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Eukaryotic organisms use conserved checkpoint mechanisms that regulate Cdk1 by inhibitory phosphorylation to prevent mitosis from interfering with DNA replication or repair. In metazoans, this checkpoint mechanism is also used for coordinating mitosis with dynamic developmental processes. Inhibitory phosphorylation of Cdk1 is catalyzed by Wee1 kinases that phosphorylate tyrosine 15 (Y15) and dual-specificity Myt1 kinases found only in metazoans that phosphorylate Y15 and the adjacent threonine (T14) residue. Despite partially redundant roles in Cdk1 inhibitory phosphorylation, Wee1 and Myt1 serve specialized developmental functions that are not well understood. Here, we expressed wild-type and phospho-acceptor mutant Cdk1 proteins to investigate how biochemical differences in Cdk1 inhibitory phosphorylation influence Drosophila imaginal development. Phosphorylation of Cdk1 on Y15 appeared to be crucial for developmental and DNA damage-induced G2-phase checkpoint arrest, consistent with other evidence that Myt1 is the major Y15-directed Cdk1 inhibitory kinase at this stage of development. Expression of non-inhibitable Cdk1 also caused chromosome defects in larval neuroblasts that were not observed with Cdk1(Y15F) mutant proteins that were phosphorylated on T14, implicating Myt1 in a novel mechanism promoting genome stability. Collectively, these results suggest that dual inhibitory phosphorylation of Cdk1 by Myt1 serves at least two functions during development. Phosphorylation of Y15 is essential for the premitotic checkpoint mechanism, whereas T14 phosphorylation facilitates accumulation of dually inhibited Cdk1-Cyclin B complexes that can be rapidly activated once checkpoint-arrested G2-phase cells are ready for mitosis.

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Section: Discussionsupporting

confidence: 75%

“…They have also been implicated in Cdk1/Cyclin B nucleo-cytoplasmic trafficking mechanisms coordinating the G2/M transition (Liu et al 1999;Wells et al 1999;Gavet and Pines 2010). These complexities have made it difficult to assign specific molecular functions to Wee1 and Myt1 kinases (Okamoto et al 2002;Burrows et al 2006;Oh et al 2010).…”

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confidence: 99%

Dual Phosphorylation of Cdk1 Coordinates Cell Proliferation with Key Developmental Processes in Drosophila

et al. 2014

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“…Myt1 activity is negatively regulated during oocyte maturation in many organisms, consistent with a role for Myt1 in inhibiting Cdk1 during meiotic G2 phase (Palmer et al 1998;Lamitina and L'Hernault 2002;Leise and Mueller 2002;Okumura et al 2002;Peter et al 2002;Inoue and Sagata 2005;Burrows et al 2006). Whether Myt1 has a role in Drosophila oocyte maturation remains unclear (Ivanovska et al 2004), however, Drosophila myt1 mutants exhibit pleiotropic cell-cycle defects during male and female gametogenesis, which suggest that dMyt1 has a role in developmentally regulated G2 phase arrest and in cell-cycle exit mechanisms that are normally coupled with terminal differentiation (Jin et al 2005).…”

mentioning

confidence: 78%

“…Further evidence of a role for Myt1 in G2/M regulation comes from studies of oocyte maturation in frogs, starfish, and nematodes (Palmer et al 1998;Okumura et al 2002;Peter et al 2002;Burrows et al 2006). Not all data indicate that Myt1 is required for G2 phase arrest, however, and there is no evidence that dMyt1 regulates oocyte maturation in Drosophila (Ivanovska et al 2004;Jin et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Drosophila Myt1 Is the Major Cdk1 Inhibitory Kinase for Wing Imaginal Disc Development

Jin¹,

Homola

Tiong

et al. 2008

Genetics

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Mitosis is triggered by activation of Cdk1, a cyclin-dependent kinase. Conserved checkpoint mechanisms normally inhibit Cdk1 by inhibitory phosphorylation during interphase, ensuring that DNA replication and repair is completed before cells begin mitosis. In metazoans, this regulatory mechanism is also used to coordinate cell division with critical developmental processes, such as cell invagination. Two types of Cdk1 inhibitory kinases have been found in metazoans. They differ in subcellular localization and Cdk1 target-site specificity: one (Wee1) being nuclear and the other (Myt1), membrane-associated and cytoplasmic. Drosophila has one representative of each: dMyt1 and dWee1. Although dWee1 and dMyt1 are not essential for zygotic viability, loss of both resulted in synthetic lethality, indicating that they are partially functionally redundant. Bristle defects in myt1 mutant adult flies prompted a phenotypic analysis that revealed cell-cycle defects, ectopic apoptosis, and abnormal responses to ionizing radiation in the myt1 mutant imaginal wing discs that give rise to these mechanosensory organs. Cdk1 inhibitory phosphorylation was also aberrant in these myt1 mutant imaginal wing discs, indicating that dMyt1 serves Cdk1 regulatory functions that are important both for normal cell-cycle progression and for coordinating mitosis with critical developmental processes.

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“…However, in the germline assembly line only the -1 oocyte undergoes maturation. MPK-1 activation thus is not sufficient and additional regulatory mechanisms, such as inhibition of CDK-1 from proximal oocytes and/or inhibition from somatic gonadal sheath cells, must block maturation of the -2 through -5 oocytes (McCarter et al 1999;Burrows et al 2006;Govindan et al 2006). We observe that levels of activated MPK-1 vary considerably in the -2 through -5 oocytes, even within the same gonad; the significance of this variability is unclear and the mechanism by which the variability is generated is not known.…”

Section: Discussionmentioning

confidence: 99%

Multiple Functions and Dynamic Activation of MPK-1 Extracellular Signal-Regulated Kinase Signaling inCaenorhabditis elegansGermline Development

Lee

Ohmachi

Arur³

et al. 2007

Genetics

169

338

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The raison d'etre of the germline is to produce oocytes and sperm that pass genetic material and cytoplasmic constituents to the next generation. To achieve this goal, many developmental processes must be executed and coordinated. ERK, the terminal MAP kinase of a number of signaling pathways, controls many aspects of development. Here we present a comprehensive analysis of MPK-1 ERK in Caenorhabditis elegans germline development. MPK-1 functions in four developmental switches: progression through pachytene, oocyte meiotic maturation/ovulation, male germ cell fate specification, and a nonessential function of promoting the proliferative fate. MPK-1 also regulates multiple aspects of cell biology during oogenesis, including membrane organization and morphogenesis: organization of pachytene cells on the surface of the gonadal tube, oocyte organization and differentiation, oocyte growth control, and oocyte nuclear migration. MPK-1 activation is temporally/spatially dynamic and most processes appear to be controlled through sustained activation. MPK-1 thus may act not only in the control of individual processes but also in the coordination of contemporaneous processes and the integration of sequential processes. Knowledge of the dynamic activation and diverse functions of MPK-1 provides the foundation for identification of upstream signaling cascades responsible for region-specific activation and the downstream substrates that mediate the various processes. I N the generation of oocytes and sperm, perhaps the most complex cells in animals, the germline lineage undergoes a multifaceted developmental process that begins in embryogenesis and continues into adulthood. While the details of the steps can differ between species due to differences in reproductive biology, a core set of events occurs in animals: germ cell fate specification, incorporation into the gonad, sexual fate specification, proliferative expansion, and gamete production. Two interconnected differentiation programs define gamete production: (1) meiosis where chromosomes pair, recombine, and then segregate to give a reassorted haploid content and (2) gametogenesis where biosynthetic and morphogenetic processes generate the large nutrient and developmental information-rich oocyte and the small motile sperm. In aggregate, these processes are essential to pass genetic material from generation to generation and to form the totipotent zygote necessary for the development of a new individual. Disruption of germline development can lead to sterility, germline tumors, and birth defects. Thus an important goal is to define the pathways and gene products that control and execute the various steps of germline development.The MAP kinase extracellular signal-regulated kinase (ERK) functions in many aspects of animal development and homeostasis (Marshall 1995;Rubin et al. 1997;Schlessinger 2000;Sundaram 2006). ERK is the terminal regulator of signaling cascades such as canonical receptor tyrosine kinase signaling, which contains core members, including the RA...

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TheC. elegansMyt1 ortholog is required for the proper timing of oocyte maturation

Cited by 75 publications

References 65 publications

Dual Phosphorylation of Cdk1 Coordinates Cell Proliferation with Key Developmental Processes in Drosophila

Dual Phosphorylation of Cdk1 Coordinates Cell Proliferation with Key Developmental Processes in Drosophila

Drosophila Myt1 Is the Major Cdk1 Inhibitory Kinase for Wing Imaginal Disc Development

Multiple Functions and Dynamic Activation of MPK-1 Extracellular Signal-Regulated Kinase Signaling inCaenorhabditis elegansGermline Development

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