ArticleProceedings of the National Academy of Sciences of the United States of America2011
Caenorhabditis elegans aristaless/Arx gene alr-1 restricts variable gene expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- sept-1/zina-1 is an ancient toxin-antidote system in Caenorhabditis elegans.PLoS biology · 2026Article
- Interlocked transcription factor feedback loops maintain and restore adult touch sensation.Cell reports · 2026Article
- Neurogenesis in Caenorhabditis elegans.Genetics · 2024Review
- MBL-1/Muscleblind regulates neuronal differentiation and controls the splicing of a terminal selector in Caenorhabditis elegans.PLoS genetics · 2024Article
- PRC1 chromatin factors strengthen the consistency of neuronal cell fate specification and maintenance in C. elegans.PLoS genetics · 2022Article
- Developmental disorders caused by haploinsufficiency of transcriptional regulators: a perspective based on cell fate determination.Biology open · 2022Article
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- Open Frontiers in Neural Cell Type Investigations; Lessons FromFrontiers in neuroscience · 2021Review
- Hmx3a Has Essential Functions in Zebrafish Spinal Cord, Ear and Lateral Line Development.Genetics · 2020Article
- Combining single-cell RNA-sequencing with a molecular atlas unveils new markers for Caenorhabditis elegans neuron classes.Nucleic acids research · 2020Article
- Histone demethylase KDM5C is a SAHA-sensitive central hub at the crossroads of transcriptional axes involved in multiple neurodevelopmental disorders.Human molecular genetics · 2019Article
- Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factors.eLife · 2019Article
- Inhibition of cell fate repressors secures the differentiation of the touch receptor neurons ofDevelopment (Cambridge, England) · 2018Article
- What's Luck Got to Do with It: Single Cells, Multiple Fates, and Biological Nondeterminism.Molecular cell · 2016Review
- Caenorhabditis elegans paraoxonase-like proteins control the functional expression of DEG/ENaC mechanosensory proteins.Molecular biology of the cell · 2016Article
- MEC-10 and MEC-19 Reduce the Neurotoxicity of the MEC-4(d) DEG/ENaC Channel in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2016Article
- Flow Cytometric Characterization of Antigen-Specific T Cells Based on RNA and Its Advantages in Detecting Infections and Immunological Disorders.Critical reviews in immunology · 2016Article
- Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation.Cell reports · 2015Article
- Hox Genes Promote Neuronal Subtype Diversification through Posterior Induction in Caenorhabditis elegans.Neuron · 2015Article
- Whole-mount single molecule FISH method for zebrafish embryo.Scientific reports · 2015Article
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
Variable expressivity of mutant phenotypes in genetically identical individuals is a phenomenon widely reported but poorly understood. For example, mutations in the gene encoding the transcription factor ALR-1 in Caenorhabditis elegans result in variable touch receptor neuron (TRN) function. Using single-molecule in situ hybridization, we demonstrate that this phenotypic variability reflects enhanced variability in the expression of the selector gene mec-3, which is needed, together with unc-86, for the differentiation of the TRNs. In a yeast expression system, ALR-1 enhances MEC-3/UNC-86-dependent transcription from the mec-3 promoter, showing that ALR-1 can enhance bulk mec-3 expression. We show that, due to stochastic fluctuations, autoregulation of mec-3 is not sufficient for TRN differentiation; ALR-1 provides a second positive feedback loop that increases mec-3 expression, by restricting variability, and thus ensures TRN differentiation. Our results link fluctuations in gene expression to phenotypic variability, which is seen in many mutant strains, and provide an explicit demonstration of how variable gene expression can be curtailed in developing cells to ensure their differentiation. Because ALR-1 and similar proteins (Drosophila Aristaless and human ARX) are needed for the expression of other transcription factors, we propose that proteins in this family may act to ensure differentiation more generally.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.