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The transmembrane LRR protein DMA-1 promotes dendrite branching and growth in C. elegans

Nature Neuroscience volume 15, pages 57–63 (2012)Cite this article

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Abstract

Dendrites often adopt complex branched structures. The development and organization of these arbors fundamentally determine the potential input and connectivity of a given neuron. The cell-surface receptors that control dendritic branching remain poorly understood. We found that, in Caenorhabditis elegans, a previously uncharacterized transmembrane protein containing extracellular leucine-rich repeat (LRR) domains, which we named DMA-1 (dendrite-morphogenesis-abnormal), promotes dendrite branching and growth. Sustained expression of dma-1 was found only in the elaborately branched sensory neurons PVD and FLP. Genetic analysis revealed that the loss of dma-1 resulted in much reduced dendritic arbors, whereas overexpression of dma-1 resulted in excessive branching. Forced expression of dma-1 in neurons with simple dendrites was sufficient to promote ectopic branching. Worms lacking dma-1 were defective in sensing harsh touch. DMA-1 is the first transmembrane LRR protein to be implicated in dendritic branching and expands the breadth of roles of LRR receptors in nervous system development.

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Figure 1: DMA-1 is expressed in highly branched neurons.
Figure 2: dma-1 positively regulates PVD branching.
Figure 3: DMA-1 functions cell autonomously.
Figure 4: dma-1 also regulates FLP branching.
Figure 5: dma-1 overexpression causes excessive branching.
Figure 6: Expression of dma-1 in morphologically simple neurons can induce ectopic branching.
Figure 7: dma-1 mutants display defects in response to harsh touch.

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Acknowledgements

We thank C. Gao and Y. Fu for technical assistance, C. Chen, K. Mizumoto, P. Chia and A. Hellman for critical reading of the manuscript, and the members of the Shen laboratory for helpful discussion. We would also like to thank the members of the Hobert and the Jorgensen laboratories for sharing plasmids and expertise regarding fosmid recombineering and MosDel. This work was supported by grants from the Howard Hughes Medical Institute and the US National Institutes of Health to K.S., and a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund to O.W.L.

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  1. Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, California, USA

    Oliver W Liu & Kang Shen

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  1. Oliver W Liu
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O.W.L. conducted the experiments. K.S. supervised the project. O.W.L. and K.S. wrote the manuscript.

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Correspondence to Kang Shen.

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Liu, O., Shen, K. The transmembrane LRR protein DMA-1 promotes dendrite branching and growth in C. elegans. Nat Neurosci 15, 57–63 (2012). https://doi.org/10.1038/nn.2978

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