Somatic polyploidization and cellular proliferation drive body size evolution in nematodes

Flemming, Anthony J.; Shen, Zai Zhong; Cunha, Ana; Emmons, Scott W.; Leroi, Armand M.

doi:10.1073/pnas.97.10.5285

Cited by 142 publications

(204 citation statements)

References 47 publications

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“…These results may also indicate Li ϩ causing some attempt to initiate DNA replication or repair. The nematodes exposed to Li ϩ were late L4 larvae (3 days old) when essentially all somatic cells are non-dividing (56), although endoreduplication of nuclear DNA is observed within a limited number of hypodermal cells (57). However, analysis of bromodeoxyuridine incorporation to identify cells undergoing DNA replication revealed no differences between untreated and Li ϩ -treated worms (data not shown).…”

Section: Discussionmentioning

confidence: 92%

Pharmacogenetic Analysis of Lithium-induced Delayed Aging in Caenorhabditis elegans

McColl

Killilea²,

Hubbard

et al. 2008

Journal of Biological Chemistry

182

145

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Lithium (Li؉ ) has been used to treat mood affect disorders, including bipolar, for decades. This drug is neuroprotective and has several identified molecular targets. However, it has a narrow therapeutic range and the one or more underlying mechanisms of its therapeutic action are not understood. Here we describe a pharmacogenetic study of Li ؉ in the nematode Caenorhabditis elegans. Exposure to Li ؉ at clinically relevant concentrations throughout adulthood increases survival during normal aging (up to 46% median increase). Longevity is extended via a novel mechanism with altered expression of genes encoding nucleosome-associated functions. Li ؉ treatment results in reduced expression of the worm ortholog of LSD-1 (T08D10.2), a histone demethylase; knockdown by RNA interference of T08D10.2 is sufficient to extend longevity (ϳ25% median increase), suggesting Li ؉ regulates survival by modulating histone methylation and chromatin structure.

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Section: Discussionmentioning

confidence: 92%

Pharmacogenetic Analysis of Lithium-induced Delayed Aging in Caenorhabditis elegans

McColl

Killilea²,

Hubbard

et al. 2008

Journal of Biological Chemistry

182

145

View full text Add to dashboard Cite

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“…The mechanism of action of IIS on body size remains to be investigated. DBL-1 TGFb signaling promotes growth by stimulating endoreduplication of hypodermal nuclei (Flemming et al, 2000). Possibly there is cross talk between IIS and DBL-1 TGFb signaling, as there is between IIS and DAF-7 TGFb signaling in the regulation of dauer larva formation (Ogg et al, 1997).…”

Section: Body Size and Lifespan In C Elegansmentioning

confidence: 99%

“…A major regulatory pathway for body size in C. elegans involves the TGFb-like ligand DBL-1, signaling via the DAF-4 and SMA-6 TGFb receptors and the SMA-2, SMA-3 and SMA-4 SMAD proteins (reviewed in Savage-Dunn (2001). Mutations in these components result in reduced body size, apparently due to a reduction in cell size rather than in cell number (Suzuki et al, 1999;Flemming et al, 2000). Mutations in lon (long) genes result in giant adults that exhibit an increased body length.…”

Section: Aging In Giant and Dwarf Mutantsmentioning

confidence: 99%

Body size, insulin/IGF signaling and aging in the nematode Caenorhabditis elegans

McCulloch

Gems

2003

Experimental Gerontology

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A number of recent studies of aging in Drosophila, mice and dogs have shown an association between reduced body size and increased lifespan. It is unclear (a) whether such an association is a general feature of animal species; and (b) whether the association reflects an effect of body size on aging, or pleiotropic effects of common determinants of growth and aging. To address these issues, we have studied the relationship between size and lifespan in the nematode Caenorhabditis elegans, and surveyed related findings in Drosophila. In C. elegans, we compared 12 wild isolates with varying body size and lifespan, but saw no correspondence between these traits. We also examined aging in giant and dwarf mutants, but observed only reduced lifespan in all cases. In a comparison of 15 long-lived daf-2 insulin/IGF receptor mutants, we saw a positive correlation between body length and lifespan, and up to a 28% increase in daf-2 mutant body volume. Thus, in C. elegans, insulin/IGF signaling may limit growth rather than promote it. Studies of Drosophila show no consistent correlation between body size and lifespan. These results indicate that the negative correlation between body size and lifespan seen in some mammals is not typical of invertebrates, but support the view that co-variation of size and longevity may occur via effects on insulin/IGF signaling. q

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“…For example, during leaf development, cells in leaf primordia actively proliferate, and the growth of leaves is often associated with a switch for most cells to begin endoreduplication with a basipetal polarity. In animals, endoreduplication has crucial roles in establishing organ and body size and in maintaining tissue or organ growth in response to stresses (Flemming et al, 2000;Lee et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The Ubiquitin Receptors DA1, DAR1, and DAR2 Redundantly Regulate Endoreduplication by Modulating the Stability of TCP14/15 in Arabidopsis

et al. 2015

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Organ growth involves the coordination of cell proliferation and cell growth with differentiation. Endoreduplication is correlated with the onset of cell differentiation and with cell and organ size, but little is known about the molecular mechanisms linking cell and organ growth with endoreduplication. We have previously demonstrated that the ubiquitin receptor DA1 influences organ growth by restricting cell proliferation. Here, we show that DA1 and its close family members DAR1 and DAR2 are redundantly required for endoreduplication during leaf development. DA1, DAR1, and DAR2 physically interact with the transcription factors TCP14 and TCP15, which repress endoreduplication by directly regulating the expression of cell-cycle genes. We also show that DA1, DAR1, and DAR2 modulate the stability of TCP14 and TCP15 proteins in Arabidopsis thaliana. Genetic analyses demonstrate that DA1, DAR1, and DAR2 function in a common pathway with TCP14/15 to regulate endoreduplication. Thus, our findings define an important genetic and molecular mechanism involving the ubiquitin receptors DA1, DAR1, and DAR2 and the transcription factors TCP14 and TCP15 that links endoreduplication with cell and organ growth.

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Somatic polyploidization and cellular proliferation drive body size evolution in nematodes

Cited by 142 publications

References 47 publications

Pharmacogenetic Analysis of Lithium-induced Delayed Aging in Caenorhabditis elegans

Pharmacogenetic Analysis of Lithium-induced Delayed Aging in Caenorhabditis elegans

Body size, insulin/IGF signaling and aging in the nematode Caenorhabditis elegans

The Ubiquitin Receptors DA1, DAR1, and DAR2 Redundantly Regulate Endoreduplication by Modulating the Stability of TCP14/15 in Arabidopsis

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