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

Nature volume 395, pages 78–82 (1998)Cite this article

Abstract

In the nematode Caenorhabditis elegans six GABAergic motor neurons, known as DDs1,2, remodel their patterns of synaptic connectivity during larval development3. 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 lineages4,5, 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.

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Figure 1: Punc-25-SNB–GFP expression reflects the pattern of DD synaptic connectivity.
Figure 2: Timing of DD synaptic remodelling.
Figure 3: Effects of lin-14 on DD synaptic remodelling.
Figure 4: Changes in LIN-14 protein levels within the DDs precede the onset of synaptic remodelling.

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Acknowledgements

We thank M. Nonet for the SNB–GFP DNA; V. Ambros and Y. Hong for lin-14 alleles and lin-14(+) genomic DNA; G. Ruvkun, B. Reinhart and F. Slack for anti-LIN-14 antibodies; and A. Chisholm, A. Zahler, J. Sisson, V. Ambros, M. Nonet, M. Zhen, I. Chin-Sang and members of the Jin and Chisholm labs for helpful discussions and comments. Some strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH Center for Research Resources. S.J.H. was supported by a Predoctoral GAANN fellowship. Y.J. is an Alfred P. Sloan Research Fellow.

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  1. Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz, Santa Cruz, 95064, California, USA

    Steven J. Hallam

  2. Yishi Jin

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Correspondence to Yishi Jin.

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Hallam, S., Jin, Y. lin-14 regulates the timing of synaptic remodelling in Caenorhabditis elegans. Nature 395, 78–82 (1998). https://doi.org/10.1038/25757

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