A Regulatory Module Controlling Pharyngeal Development and Function in <i>Caenorhabditis elegans</i>

Fay, David S.; Polley, Stanley R. G.; Kuang, Jujiao; Kuzmanov, Aleksandra; Hazel, James W.; Mani, Kumaran; Veo, Bethany; Yochem, John

doi:10.1534/genetics.112.140814

Cited by 8 publications

(37 citation statements)

References 32 publications

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“…In addition, the synthetic lethality of ari-1 (tm2549); pha-1(ts) mutants at 16°was also suppressed by sup-36(RNAi) ( Table 1). These findings are consistent with genetic suppression data previously obtained for sup-35 and sup-37 and further link these three suppressors to a common cellular function (Qiu and Fay 2006;Mani and Fay 2009;Fay et al 2012). Furthermore, we find that similar to LOF mutations in sup-35 and sup-37 , loss of sup-36 suppressed two null deletion alleles of pha-1 (tm3671 and tm3569) (Table 1).…”

Section: Resultssupporting

confidence: 92%

“…Notably, LOF mutations in sup-35 and sup-37 completely suppress the lethality of pha-1 LOF mutants, including several molecular nulls (Schnabel et al 1991;Mani and Fay 2009;Fay et al 2012). This observation, together with other data, has led to the hypothesis that SUP-35 and SUP-37 act in a pathway or complex that is in opposition to PHA-1, possibly through the regulation of a mutual downstream target or biological processes.…”

mentioning

confidence: 87%

“…sup-35 is regulated at the level of transcription by LIN-35 and HCF-1 (Mani and Fay 2009;Fay et al 2012). Specifically, LIN-35 functions as a negative regulator of sup-35 expression, whereas HCF-1 promotes sup-35 transcription.…”

Section: Regulation Of Sup-36 By Upstream Factorsmentioning

confidence: 99%

“…LIN-35 and UBC-18-ARI-1 negatively regulate a Zn-finger protein, SUP-35/ZTF-21, at the level of transcription and protein stability, respectively (Mani and Fay 2009). Furthermore, SUP-35, along with a second Zn-finger protein, SUP-37/ZTF-12, functionally opposes PHA-1, a novel cytoplasmic protein that is required for C. elegans embryonic development (Schnabel and Schnabel 1990;Granato et al 1994;Fay et al 2004Fay et al , 2012. Our working model is that in the absence of both lin-35 and ubc-18 activities, SUP-35 levels are abnormally elevated, which in turn interferes with the ability of PHA-1 to carry out essential functions during embryogenesis.…”

mentioning

confidence: 99%

“…Loss-of-function (LOF) mutations in pha-1 lead to gross defects in pharyngeal development and body morphology (Schnabel and Schnabel 1990;Fay et al 2004Fay et al , 2012. Specifically, PHA-1 plays a role in both establishing and maintaining a stable attachment between the anterior epithelial cells of the developing pharynx and the arcade cells that compose the future buccal cavity (mouth) (Fay et al 2004).…”

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confidence: 99%

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Implicating SCF Complexes in Organogenesis in Caenorhabditis elegans

Polley¹,

Kuzmanov²,

Kuang³

et al. 2014

Genetics

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Development of the Caenorhabditis elegans foregut (pharynx) is regulated by a network of proteins that includes the Retinoblastoma protein (pRb) ortholog LIN-35; the ubiquitin pathway components UBC-18 and ARI-1; and PHA-1, a cytoplasmic protein. Loss of pha-1 activity impairs pharyngeal development and body morphogenesis, leading to embryonic arrest. We have used a genetic suppressor approach to dissect this complex pathway. The lethality of pha-1 mutants is suppressed by loss-of-function mutations in sup-35/ztf-21 and sup-37/ztf-12, which encode Zn-finger proteins, and by mutations in sup-36. Here we show that sup-36 encodes a divergent Skp1 family member that binds to several F-box proteins and the microtubule-associated protein PLT-1/t. Like SUP-35, SUP-36 levels were negatively regulated by UBC-18-ARI-1. We also found that SUP-35 and SUP-37 physically associated and that SUP-35 could bind microtubules. Thus, SUP-35, SUP-36, and SUP-37 may function within a pathway or complex that includes cytoskeletal components. Additionally, SUP-36 may regulate the subcellular localization of SUP-35 during embryogenesis. We carried out a genome-wide RNAi screen to identify additional regulators of this network and identified 39 genes, most of which are associated with transcriptional regulation. Twenty-three of these genes acted via the LIN-35 pathway. In addition, several S-phase kinaseassociated protein (Skp)1-Cullin-F-Box (SCF) components were identified, further implicating SCF complexes as part of the greater network controlling pharyngeal development.

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Section: Resultssupporting

confidence: 92%

mentioning

confidence: 87%

Section: Regulation Of Sup-36 By Upstream Factorsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Implicating SCF Complexes in Organogenesis in Caenorhabditis elegans

Polley¹,

Kuzmanov²,

Kuang³

et al. 2014

Genetics

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Genetics: Master Regulator or Master of Disguise?

Ailion

Malik

2017

Current Biology

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A maternal-effect genetic incompatibility inCaenorhabditis elegans

Ben-David

Burga

Kruglyak

2017

Preprint

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(L.K.).* These authors contributed equally to this work.Selfish genetic elements spread in natural populations and have an important role in genome evolution. We discovered a selfish element causing a genetic incompatibility between strains of the nematode Caenorhabditis elegans. The element is made up of sup-35, a maternal-effect toxin that kills developing embryos, and pha-1, its zygotically expressed antidote. pha-1 has long been considered essential for pharynx development based on its mutant phenotype, but this phenotype in fact arises from a loss of suppression of sup-35 toxicity. Inactive copies of the sup-35/pha-1 element show high sequence divergence from active copies, and phylogenetic reconstruction suggests that they represent ancestral stages in the evolution of the element. Our results suggest that other essential genes identified by genetic screens may turn out to be components of selfish elements.. CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/112524 doi: bioRxiv preprint first posted online Feb. 28, 2017; 2 IntroductionSelfish genetic elements subvert the laws of Mendelian segregation to promote their own transmission (Dawkins 1976;Doolittle and Sapienza 1980;Orgel and Crick 1980;Werren 2011;Sinkins 2011). In what is perhaps the most extreme scenario, selfish elements can kill individuals that do not inherit them, leading to a genetic incompatibility between carriers and non-carriers (Beeman et al. 1992;Werren 1997Werren , 2011Hurst and Werren 2001;Lorenzen et al. 2008). Selfish elements are predicted to spread in natural populations (Hurst and Werren 2001;Werren 2011), and consequently, there is significant interest in using synthetic forms of such elements to drive population replacement of pathogen vectors in the wild (Chen et al. 2007;Hammond et al. 2015). However, despite the prominent role of genetic incompatibilities in genome evolution and their promise in pathogen control, their underlying genetic mechanisms have been resolved in only a few cases (Werren 2011). Our laboratory previously identified the only known genetic incompatibility in the nematode Caenorhabditis elegans (Seidel et al. 2008(Seidel et al. , 2011. The incompatibility is caused by a selfish element composed of two tightly linked genes: peel-1, a sperm-delivered toxin, and zeel-1, a zygotically expressed antidote. In crosses between isolates that carry the element and ones that do not, the peel-1 toxin is delivered by the sperm to all progeny, so that only embryos that inherit the element and the zeel-1 antidote survive. An analogous element, Maternal-effect dominant embryonic arrest (Medea) has been previously described in the beetle Tribolium; however, the underlying genes remain unknown (Beeman et al. 1992;Lorenzen et al. 2008). Results A maternal-effect genetic incompatibility in C. elegansAs part of ongoing efforts to study natural genetic variation in C. elegans, we introgr...

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A Regulatory Module Controlling Pharyngeal Development and Function in Caenorhabditis elegans

Cited by 8 publications

References 32 publications

Implicating SCF Complexes in Organogenesis in Caenorhabditis elegans

Implicating SCF Complexes in Organogenesis in Caenorhabditis elegans

Genetics: Master Regulator or Master of Disguise?

A maternal-effect genetic incompatibility inCaenorhabditis elegans

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