lin-14 regulates the timing of synaptic remodelling in Caenorhabditis elegans

Nature. 1998 Sep 3;395(6697):78-82. doi: 10.1038/25757.


In the nematode Caenorhabditis elegans six GABAergic motor neurons, known as DDs, remodel their patterns of synaptic connectivity during larval development. DD remodelling involves a complete reversal of the direction of information flow within nerve processes without marked changes in process morphology. We used a marker localized in vivo to DD presynaptic zones to analyse how the timing of DD remodelling is controlled. In wild-type animals, DDs remodel their synaptic outputs within a 3-5-hour period at the end of the first larval stage. We show that the heterochronic gene lin-14, which controls the timing of stage-specific cell lineages, regulates the timing of DD synaptic output remodelling. In lin-14 loss-of-function mutants, DDs remodel precociously. The degree of precocious remodelling is correlated with the level of lin-14 activity. Expression of lin-14(+) in the DDs of lin-14-null mutants rescues the precocious remodelling, indicating that lin-14 can act cell-autonomously. Consistent with this hypothesis, LIN-14 protein levels decrease in the DDs before remodelling. Our observations reveal a role of heterochronic genes in non-dividing cells, and provide an example of cell-autonomous respecification of neuronal connectivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins*
  • Cell Polarity
  • Glutamate Decarboxylase / genetics
  • Helminth Proteins / genetics
  • Helminth Proteins / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Motor Neurons / physiology*
  • Nuclear Proteins*
  • Synapses / physiology*


  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • LIN-14 protein, C elegans
  • Membrane Proteins
  • Nuclear Proteins
  • Glutamate Decarboxylase