Embryonic priming of a miRNA locus predetermines postmitotic neuronal left/right asymmetry in C. elegans

Cell. 2012 Dec 7;151(6):1229-42. doi: 10.1016/j.cell.2012.10.049. Epub 2012 Nov 29.


The mechanisms by which functional left/right asymmetry arises in morphologically symmetric nervous systems are poorly understood. Here, we provide a mechanistic framework for how functional asymmetry in a postmitotic neuron pair is specified in C. elegans. A key feature of this mechanism is a temporally separated, two-step activation of the lsy-6 miRNA locus. The lsy-6 locus is first "primed" by chromatin decompaction in the precursor for the left neuron, but not the right neuron, several divisions before the neurons are born. lsy-6 expression is then "boosted" to functionally relevant levels several divisions later in the mother of the left neuron, through the activity of a bilaterally expressed transcription factor that can only activate lsy-6 in the primed neuron. This study shows how cells can become committed during early developmental stages to execute a specific fate much later in development and provides a conceptual framework for understanding the generation of neuronal diversity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Body Patterning*
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism
  • Cell Lineage
  • Embryo, Nonmammalian / metabolism
  • Gene Expression
  • MicroRNAs / metabolism
  • Neurons / cytology*
  • Neurons / metabolism
  • Receptors, Notch / metabolism
  • Sequence Alignment


  • MIRNLsy-6 microRNA, C elegans
  • MicroRNAs
  • Receptors, Notch