MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision
| Autor: | Oliver Hobert, Sarah Chang, John F. Etchberger, Robert J. Johnston, Christopher O. Ortiz |
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| Rok vydání: | 2005 |
| Předmět: |
Cellular differentiation
Gene regulatory network Biology Cell fate determination medicine.disease_cause Models Biological Feedback Receptors G-Protein-Coupled Animals Genetically Modified Network motif medicine Animals Caenorhabditis elegans Transcription factor Genes Helminth Neurons Genetics Mutation Multidisciplinary Gene Expression Regulation Developmental Cell Differentiation Biological Sciences biology.organism_classification Chemoreceptor Cells MicroRNAs Neuroscience Developmental biology |
| Zdroj: | Proceedings of the National Academy of Sciences. 102:12449-12454 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0505530102 |
| Popis: | The elucidation of the architecture of gene regulatory networks that control cell-type specific gene expression programs represents a major challenge in developmental biology. We describe here a cell fate decision between two alternative neuronal fates and the architecture of a gene regulatory network that controls this cell fate decision. The two Caenorhabditis elegans taste receptor neurons “ASE left” (ASEL) and “ASE right” (ASER) share many bilaterally symmetric features, but each cell expresses a distinct set of chemoreceptors that endow the gustatory system with the capacity to sense and discriminate specific environmental inputs. We show that these left/right asymmetric fates develop from a precursor state in which both ASE neurons express equivalent features. This hybrid precursor state is unstable and transitions into the stable ASEL or ASER terminal end state. Although this transition is spatially stereotyped in wild-type animals, mutant analysis reveals that each cell has the potential to transition into either the ASEL or ASER stable end state. The stability and irreversibility of the terminal differentiated state is ensured by the interactions of two microRNAs (miRNAs) and their transcription factor targets in a double-negative feedback loop. Simple feedback loops are found as common motifs in many gene regulatory networks, but the loop described here is unusually complex and involves miRNAs. The interaction of miRNAs in double-negative feedback loops may not only be a means for miRNAs to regulate their own expression but may also represent a general paradigm for how terminal cell fates are selected and stabilized. |
| Databáze: | OpenAIRE |
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