Journal
DEVELOPMENT
Volume 132, Issue 24, Pages 5451-5460Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.02163
Keywords
C. elegans; chemosensory neurons; laterality; fate determination; microRNA
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Funding
- NINDS NIH HHS [R01 NS050266-01, NS39996-05, R01 NS050266, R01 NS050266-05] Funding Source: Medline
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The two Caenorhabditis elegans gustatory neurons, ASE left (ASEL) and ASE right (ASER) are morphologically bilaterally symmetric, yet left/right asymmetric in function and in the expression of specific chemosensory signaling molecules. The ASEL versus ASER cell-fate decision is controlled by a complex gene regulatory network composed of microRNAs (miRNAs) and transcription factors. Alterations in the activities of each of these regulatory factors cause a complete lateral cell-fate switch. Here, we describe lsy-2, a novel C2H2 zinc finger transcription factor that is required for the execution of the ASEL stable state. In lsy-2 null mutants, the ASEL neuron adopts the complete ASER gene expression profile, including both upstream regulatory and terminal effector genes. The normally left/right asymmetric ASE neurons are therefore 'symmetrized' in lsy-2 mutants. Cell-specific rescue experiments indicate that lsy-2 is required autonomously in ASEL for the activation of ASEL-specifying factors and the repression of ASER-specifying factors. Genetic epistasis experiments demonstrate that lsy-2 exerts its activity by regulating the transcription of the lsy-6 miRNA in the ASEL neuron, thereby making lsy-2 one of the few factors known to control the cell-type specificity of miRNA gene expression.
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