Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the <i>C. elegans</i> germline

Fox, Paul M.; Vought, Valarie E.; Hanazawa, Momoyo; Maine, Eleanor M.; Schedl, Tim

doi:10.1242/dev.059535

Cited by 159 publications

(344 citation statements)

References 64 publications

(85 reference statements)

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“…In contrast to regulation of cycling of invertebrate C. elegans and Drosophila premeiotic GSCs, where a G1 is nearly absent and Cyclin E is expressed throughout the cycle, 18,21 we show that O. dioica, pre-meiotic, germline nuclei have a G1-phase. During the period of syncytial germline nuclear proliferation, both the Cyclin Db and Dd variants are expressed.…”

Section: Discussioncontrasting

confidence: 86%

“…18,19,21 The O. dioica Cyclin D variants, Da, Db, Dc and Dd are encoded by 4 different genes. 24 Previously, we have shown that O. dioica Cyclin Dd regulates G1-phase in mitotically proliferating cells during early development and in post-metamorphic somatic endocycling cells.…”

Section: Asynchronously Proliferating O Dioica Germ Nuclei Have a DImentioning

confidence: 99%

“…[18][19][20][21] In this context, cell cycle profiles of Cyclin E-CDK activity are altered with Cyclin E present throughout the GSC cell cycle. 18,21 In these invertebrates, proliferative renewal of GSCs is nonetheless still responsive to insulin and TOR signaling 2,22 but these nutrient-dependent controls operate during G2, as opposed to G1. In contrast, mouse spermatogonial stem cells proliferate with a distinct G1 phase and Cyclin D plays a major role in the renewal of stem cells.…”

Section: Introductionmentioning

confidence: 99%

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Co-expressed Cyclin D variants cooperate to regulate proliferation of germline nuclei in a syncytium

2015

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The role of the G1-phase Cyclin D-CDK 4/6 regulatory module in linking germline stem cell (GSC) proliferation to nutrition is evolutionarily variable. In invertebrate Drosophila and C. elegans GSC models, G1 is nearly absent and Cyclin E is expressed throughout the cell cycle, whereas vertebrate spermatogonial stem cells have a distinct G1 and Cyclin D1 plays an important role in GSC renewal. In the invertebrate, chordate, Oikopleura, where germline nuclei proliferate asynchronously in a syncytium, we show a distinct G1-phase in which 2 Cyclin D variants are co-expressed. Cyclin Dd, present in both somatic endocycling cells and the germline, localized to germline nuclei during G1 before declining at G1/S. Cyclin Db, restricted to the germline, remained cytoplasmic, co-localizing in foci with the Cyclin-dependent Kinase Inhibitor, CKIa. These foci showed a preferential spatial distribution adjacent to syncytial germline nuclei at G1/S. During nutrient-restricted growth arrest, upregulated CKIa accumulated in arrested somatic endoreduplicative nuclei but did not do so in germline nuclei. In the latter context, Cyclin Dd levels gradually decreased. In contrast, the Cyclin Dbb splice variant, lacking the Rb-interaction domain and phosphodegron, was specifically upregulated and the number of cytoplasmic foci containing this variant increased. This upregulation was dependent on stress response MAPK p38 signaling. We conclude that under favorable conditions, Cyclin Dbb-CDK6 sequesters CKIa in the cytoplasm to cooperate with Cyclin Dd-CDK6 in promoting germline nuclear proliferation. Under nutrient-restriction, this sequestration function is enhanced to permit continued, though reduced, cycling of the germline during somatic growth arrest.

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Section: Discussioncontrasting

confidence: 86%

Section: Asynchronously Proliferating O Dioica Germ Nuclei Have a DImentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Co-expressed Cyclin D variants cooperate to regulate proliferation of germline nuclei in a syncytium

2015

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“…Indeed this number, initially measured by the number of corpses observed at a given time in relation to the number of oocytes that are laid, might be even higher. More recent estimates of germ cell proliferation rates indicate that approximately 20 germ cells are produced every hour, while only ~3 oocytes are laid (Fox et al 2011 ) . Apoptosis only occurs in the female and not in the male germline and is thus only present in hermaphrodites (Gumienny et al 1999 ;Gartner et al 2000 ; ) .…”

Section: Elegans Germ Cell Apoptosismentioning

confidence: 99%

Germ Cell Apoptosis and DNA Damage Responses

Bailly

Gartner

2012

Advances in Experimental Medicine and Biology

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In the past 12 years, since the fi rst description of C. elegans germ cell apoptosis, this area of research rapidly expanded. It became evident that multiple genetic pathways lead to the apoptotic demise of germ cells. We are only beginning to understand how these pathways that all require the CED-9/Bcl-2, Apaf-1/CED-4 and CED-3 caspase core apoptosis components are regulated. Physiological apoptosis, which likely accounts for the elimination of more than 50% of all germ cells, even in unperturbed conditions, is likely to be required to maintain tissue homeostasis. The best-studied pathways lead to DNA damage-induced germ cell apoptosis in response to a variety of genotoxic stimuli. This apoptosis appears to be regulated similar to DNA damage-induced apoptosis in the mouse germ line and converges on p53 family transcription factors. DNA damage response pathways not only lead to apoptosis induction, but also directly affect DNA repair, and a transient cell cycle arrest of mitotic germ cells. Finally, distinct pathways activate germ cell apoptosis in response to defects in meiotic recombination and meiotic chromosome pairing.

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“…Moreover, it supports a differential requirement of GLP-1 activity in cells of the proliferative region. 34 Nonetheless, most likely other target mRNAs of GLD-4-mediated translational activation in transit-amplifying cells and/or GSCs exist.…”

Section: Gld-4 Promotes Proliferationmentioning

confidence: 99%