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Wnt Signaling Drives Ectopic Gene Expression and Larval Arrest in the Absence of the Caenorhabditis elegans DREAM Repressor Complex.

ABSTRACT: Establishment and maintenance of proper gene expression is a requirement for normal growth and development. The DREAM complex in Caenorhabditis elegans functions as a transcriptional repressor of germline genes in somatic cells. At 26°, DREAM complex mutants show increased misexpression of germline genes in somatic cells and High Temperature Arrest (HTA) of worms at the first larval stage. To identify transcription factors required for the ectopic expression of germline genes in DREAM complex mutants, we conducted an RNA interference screen against 123 transcription factors capable of binding DREAM target promoter loci for suppression of the HTA phenotype in lin-54 mutants. We found that knock-down of 15 embryonically expressed transcription factors suppress the HTA phenotype in lin-54 mutants. Five of the transcription factors found in the initial screen have associations with Wnt signaling pathways. In a subsequent RNAi suppression screen of Wnt signaling factors we found that knock-down of the non-canonical Wnt/PCP pathway factors vang-1, prkl-1 and fmi-1 in a lin-54 mutant background resulted in strong suppression of the HTA phenotype. Animals mutant for both lin-54 and vang-1 showed almost complete suppression of the HTA phenotype, pgl-1 misexpression, and fertility defects associated with lin-54 single mutants at 26°. We propose a model whereby a set of embryonically expressed transcription factors, and the Wnt/PCP pathway, act opportunistically to activate DREAM complex target genes in somatic cells of DREAM complex mutants at 26°.

SUBMITTER: Cherian JR

PROVIDER: S-EPMC7003081 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Wnt Signaling Drives Ectopic Gene Expression and Larval Arrest in the Absence of the <i>Caenorhabditis elegans</i> DREAM Repressor Complex.

Cherian Jerrin R JR Adams Katherine V KV Petrella Lisa N LN

G3 (Bethesda, Md.) 20200206 2

Establishment and maintenance of proper gene expression is a requirement for normal growth and development. The DREAM complex in <i>Caenorhabditis elegans</i> functions as a transcriptional repressor of germline genes in somatic cells. At 26°, DREAM complex mutants show increased misexpression of germline genes in somatic cells and High Temperature Arrest (HTA) of worms at the first larval stage. To identify transcription factors required for the ectopic expression of germline genes in DREAM com ...[more]

PMID: 31843805

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Project description:The nematode Caenorhabditis elegans responds to overcrowding and scarcity of food by arresting development as a dauer larva, a nonfeeding, long-lived, stress-resistant, alternative third-larval stage. Previous work has shown that mutations in the genes daf-2 (encoding a member of the insulin receptor family) and age-1 (encoding a PI 3-kinase) result in constitutive formation of dauer larvae (Daf-c), increased adult longevity (Age), and increased intrinsic thermotolerance (Itt). Some daf-2 mutants have additional developmental, behavioral, and reproductive defects. We have characterized in detail 15 temperature-sensitive and 1 nonconditional daf-2 allele to investigate the extent of daf-2 mutant defects and to examine whether specific mutant traits correlate with each other. The greatest longevity seen in daf-2 mutant adults was approximately three times that of wild type. The temperature-sensitive daf-2 mutants fell into two overlapping classes, including eight class 1 mutants, which are Daf-c, Age, and Itt, and exhibit low levels of L1 arrest at 25.5 degrees. Seven class 2 mutants also exhibit the class 1 defects as well as some or all of the following: reduced adult motility, abnormal adult body and gonad morphology, high levels of embryonic and L1 arrest, production of progeny late in life, and reduced brood size. The strengths of the Daf-c, Age, and Itt phenotypes largely correlated with each other but not with the strength of class 2-specific defects. This suggests that the DAF-2 receptor is bifunctional. Examination of the null phenotype revealed a maternally rescued egg, L1 lethal component, and a nonconditional Daf-c component. With respect to the Daf-c phenotype, the dauer-defective (Daf-d) mutation daf-12(m20) was epistatic to daf-2 class 1 alleles but not the severe class 2 alleles tested. All daf-2 mutant defects were suppressed by the daf-d mutation daf-16(m26). Our findings suggest a new model for daf-2, age-1, daf-12, and daf-16 interactions.

Dataset Information

Wnt Signaling Drives Ectopic Gene Expression and Larval Arrest in the Absence of the Caenorhabditis elegans DREAM Repressor Complex.

Publications

Wnt Signaling Drives Ectopic Gene Expression and Larval Arrest in the Absence of the <i>Caenorhabditis elegans</i> DREAM Repressor Complex.

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