Cki-1 links cell division and cell fate acquisition in the C. elegans somatic gonad

Kostić, Ivana T.; Li, Shaolin; Roy, Richard

doi:10.1016/j.ydbio.2003.07.001

Cited by 46 publications

(46 citation statements)

References 34 publications

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“…All other techniques, such as microscopy (Kostic et al, 2003), adult longevity and dauer formation assays (both at 25°C) (Hertweck et al, 2004), laser ablation, aak-1 RNAi (Kostic et al, 2003), and aak-2 RNAi , were performed as previously described.…”

Section: Dauer Recovery Assaymentioning

confidence: 99%

Inhibition of germline proliferation duringC. elegansdauer development requires PTEN, LKB1 and AMPK signalling

2006

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In C. elegans, reduced insulin-like signalling induces developmental quiescence, reproductive delay and lifespan extension. We show here that the C. elegans orthologues of LKB1 and AMPK cooperate during conditions of reduced insulin-like signalling to establish cell cycle quiescence in the germline stem cell population, in addition to prolonging lifespan. The inactivation of either protein causes aberrant germline proliferation during diapause-like 'dauer' development, whereas the loss of AMPK uncouples developmental arrest from lifespan extension. Reduced TGF-␤ activity also triggers developmental quiescence independent of the insulin-like pathway. Our data suggest that these two signalling pathways converge on the C. elegans PTEN orthologue to coordinate germline proliferation with somatic development during dauer formation, via the regulation of AMPK and its upstream activator LKB1, rather than through the canonical insulin-like signalling cascade. In humans, germline mutations in TGF-␤ family members, PTEN or LKB1 result in related tumour-predisposing syndromes. Our findings establish a developmental relationship that may underscore their shared, characteristic aetiology.

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Section: Dauer Recovery Assaymentioning

confidence: 99%

Inhibition of germline proliferation duringC. elegansdauer development requires PTEN, LKB1 and AMPK signalling

2006

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“…This additional round of intestinal cell division indicates a misregulation of the cell-cycle exit and mimics the embryonic phenotypes caused by cki-1 loss-of-function mutations rather than those of cdc-25.1 gain-of-function mutants where cells divide much faster (Clucas et al 2002;Kostić and Roy 2002). This fact, and the somatic gonad phenotypes caused by the inactivation of cki-1 (Kostić et al 2003;Fujita et al 2007), suggest that ham-3, swsn-2.2, and the G1/S inhibitor cki-1 may be functionally related in more than one developmental process.…”

Section: Cell-cycle Controlmentioning

confidence: 98%

Functional Interplay of Two Paralogs Encoding SWI/SNF Chromatin-Remodeling Accessory Subunits DuringCaenorhabditis elegansDevelopment

et al. 2016

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SWI/SNF ATP-dependent chromatin-remodeling complexes have been related to several cellular processes such as transcription, regulation of chromosomal stability, and DNA repair. The Caenorhabditis elegans gene ham-3 (also known as swsn-2.1) and its paralog swsn-2.2 encode accessory subunits of SWI/SNF complexes. Using RNA interference (RNAi) assays and diverse alleles we investigated whether ham-3 and swsn-2.2 have different functions during C. elegans development since they encode proteins that are probably mutually exclusive in a given SWI/SNF complex. We found that ham-3 and swsn-2.2 display similar functions in vulva specification, germline development, and intestinal cell proliferation, but have distinct roles in embryonic development. Accordingly, we detected functional redundancy in some developmental processes and demonstrated by RNA sequencing of RNAi-treated L4 animals that ham-3 and swsn-2.2 regulate the expression of a common subset of genes but also have specific targets. Cell lineage analyses in the embryo revealed hyper-proliferation of intestinal cells in ham-3 null mutants whereas swsn-2.2 is required for proper cell divisions. Using a proteomic approach, we identified SWSN-2.2-interacting proteins needed for early cell divisions, such as SAO-1 and ATX-2, and also nuclear envelope proteins such as MEL-28. swsn-2.2 mutants phenocopy mel-28 loss-of-function, and we observed that SWSN-2.2 and MEL-28 colocalize in mitotic and meiotic chromosomes. Moreover, we demonstrated that SWSN-2.2 is required for correct chromosome segregation and nuclear reassembly after mitosis including recruitment of MEL-28 to the nuclear periphery.KEYWORDS SWI/SNF; Caenorhabditis elegans; chromatin; development; nuclear envelope C HROMATIN is a dynamic structure required not only for the packaging of large amounts of DNA in the limited space of eukaryotic nuclei, but also for the regulation of gene expression (Ho and Crabtree 2010;Narlikar et al. 2013). SWI/SNF complexes, which are conserved from yeast to mammals, modify the state of the chromatin in an ATPdependent manner and, therefore, the accessibility of distinct proteins to a given DNA region (Hargreaves and Crabtree 2011;Euskirchen et al. 2012). Such activity in the DNA regulates various cellular aspects like proliferation, differentiation, chromosomal stability, and DNA repair (Reisman et al. 2009;Lans et al. 2010;Euskirchen et al. 2011). SWI/SNF complexes are involved in gene-specific regulation since only a low percentage of gene expression (6% in budding yeast, 7.5% in Caenorhabditis elegans) is regulated by these complexes (Holstege et al. 1998;Riedel et al. 2013).A canonical SWI/SNF complex consists of a central ATPase subunit, two or three core components, and several (five to eight) accessory subunits (Hargreaves and Crabtree 2011). While all SWI/SNF complexes include core subunits that are in charge of remodeling nucleosomes (Phelan et al. 1999), the accessory proteins confer specificity to a given complex and their presence varies depending on the ...

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“…Microscopy and double-strand RNA (dsRNA) injections were performed as described previously (Kostic et al 2003). Feeding RNAi (Kamath and Ahringer 2003), antibody staining, DAPI staining, germ cell nuclei counts, and dauer survival assays were all carried out as previously described (Narbonne and Roy 2006).…”

Section: Other Techniquesmentioning

confidence: 99%

Developmental and Cell Cycle Quiescence Is Mediated by the Nuclear Hormone Receptor Coregulator DIN-1S in the Caenorhabditis elegans Dauer Larva

Colella¹,

Li²,

Roy

2016

Genetics

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When faced with suboptimal growth conditions, Caenorhabditis elegans larvae can enter a diapause-like stage called "dauer" that is specialized for dispersal and survival. The decision to form a dauer larva is controlled by three parallel signaling pathways, whereby a compromise of TGFb, cyclic guanosine monophosphate, or insulin/IGF-like signaling (ILS) results in dauer formation. Signals from these pathways converge on DAF-12, a nuclear hormone receptor that triggers the changes required to initiate dauer formation. DAF-12 is related to the vitamin D, liver-X, and androstane receptors, and like these human receptors, it responds to lipophilic hormone ligands. When bound to its ligand, DAF-12 acquires transcriptional activity that directs reproductive development, while unliganded DAF-12 forms a dauer-specifying complex with its interacting protein DIN-1S to regulate the transcription of genes required for dauer development. We report here that din-1S is required in parallel to par-4/LKB1 signaling within the gonad to establish cell cycle quiescence during the onset of the dauer stage. We show that din-1S is important for postdauer reproduction when ILS is impaired and is necessary for long-term dauer survival in response to reduced ILS. Our work uncovers several previously uncharacterized functions of DIN-1S in executing and maintaining many of the cellular and physiological processes required for appropriate dauer arrest, while also shedding light on the coordination of nuclear hormone signaling, the LKB1/AMPK signaling cascade, and ILS/TGFb in the control of cell cycle quiescence and tissue growth: a key feature that is often misregulated in a number of hormone-dependent cancers. KEYWORDS quiescence; dauer; nuclear hormone receptor; insulin-like signaling; DAF-12; DIN-1S; par-4/LKB1; aak-2/AMPK L IKE many metazoans, Caenorhabditis elegans develops through a lengthy juvenile phase before reaching reproductive maturity; a process that includes the passage through four larval stages (L1-L4) to finally give rise to an adult hermaphrodite. However, if environmental conditions are inadequate for reproductive development, C. elegans possesses an effective means of modifying its life cycle allowing it to opt for an alternative mode of development referred to as the dauer stage. Dauer is a diapause-like stage that is specialized for dispersal and survival, where instead of progressing from the L2 to the L3 stage, L1 larvae will execute an alternative L2 stage (L2d) during which they alter their metabolic program to accumulate lipid reserves and subsequently enter the dauer stage (Kimura et al. 1997;Burnell et al. 2005). Dauer larvae are morphologically, metabolically, and behaviorally distinct from L3 stage larvae, while they exhibit a global state of cell cycle and developmental quiescence, presumably to conserve energy resources.The decision to form the dauer larva is controlled by three parallel signaling pathways whereby the reduction in TGFb, cyclic guanosine monophosphate or insulin/IGF-like signaling (...

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Cki-1 links cell division and cell fate acquisition in the C. elegans somatic gonad

Cited by 46 publications

References 34 publications

Inhibition of germline proliferation duringC. elegansdauer development requires PTEN, LKB1 and AMPK signalling

Inhibition of germline proliferation duringC. elegansdauer development requires PTEN, LKB1 and AMPK signalling

Functional Interplay of Two Paralogs Encoding SWI/SNF Chromatin-Remodeling Accessory Subunits DuringCaenorhabditis elegansDevelopment

Developmental and Cell Cycle Quiescence Is Mediated by the Nuclear Hormone Receptor Coregulator DIN-1S in the Caenorhabditis elegans Dauer Larva

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