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A LIM-homeodomain combinatorial code for motor-neuron pathway selection

Nature volume 397, pages 76–80 (1999)Cite this article

Abstract

Different classes of vertebrate motor neuron that innervate distinct muscle targets express unique combinations of LIM-homeodomain transcription factors1,2, suggesting that a combinatorial code of LIM-homeodomain proteins may underlie the control of motor-neuron pathway selection. Studies of LIM-homeodomain genes in mouse, Drosophila melanogaster and Caenorhabditis elegans have revealed functions of these genes in neuronal survival, axon guidance, neurotransmitter expression and neuronal function3,4,5,6,7,8, but, to our knowledge, none of these studies have addressed the issue of a functional code. Here we study two members of this gene family in Drosophila, namely lim3, the homologue of the vertebrate Lhx3 and Lhx4 genes, and islet, thehomologue of the vertebrate Isl1 and Isl2 genes. We show that Drosophila lim3 is expressed by a specific subset of islet-expressing motor neurons and that mutating or misexpressing lim3 switches motor-neuron projections predictably. Our results provide evidence that lim3 and islet constitute a combinatorial code that generates distinct motor-neuron identities.

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Figure 1: Molecular analysis of the lim3 gene.
Figure 2: Embryonic expression of lim3.
Figure 3: lim3 expression overlaps with isl but not ap expression.
Figure 4: Defects in motor-neuron pathfinding in lim3 mutants.
Figure 5: lim3 misexpression changes motor-neuron projections.
Figure 6: Conservation of expression patterns of LIM-homeodomain proteins between Drosophila and mouse.

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Acknowledgements

We thank C. S. Goodman for the ftzng-GAL4 flies and anti-fasciclin II antibody; S.Yoshikawa for the UAS-tau-myc-GFP flies; the Midamerica, Umea and Bloomington Stock Centers for providing fly stocks; L. W. Jurata and G. N. Gill for sharing unpublished results; K. Bishop and members of our laboratory for providing advice and technical assistance; and S. Pfaff, K. Sharma, G.Lemke and D. van Meyel for critical review of the manuscript. This work was supported by grants from the NIH and a Pew Scholars Award from the Pew Memorial Trusts (to J.B.T.), an EMBO Long Term Fellowship (to S.G.E.A.) and an HFSP Long-term Fellowship (to S.T.).

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Authors and Affiliations

  1. Molecular Neurobiology Laboratory, The Salk Institute, PO Box 85800, San Diego, 92186, California, USA

    Stefan Thor & John B. Thomas

  2. Department of Genetics and Development, Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, 701 West 168th Street, New York, 10032, New York, USA

    Siv G. E. Andersson & Andrew Tomlinson

  3. Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Stefan Thor

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Thor, S., Andersson, S., Tomlinson, A. et al. A LIM-homeodomain combinatorial code for motor-neuron pathway selection. Nature 397, 76–80 (1999). https://doi.org/10.1038/16275

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