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Genetics. Nov 1993; 135(3): 741–753.
PMCID: PMC1205717

Dominant Unc-37 Mutations Suppress the Movement Defect of a Homeodomain Mutation in Unc-4, a Neural Specificity Gene in Caenorhabditis Elegans

Abstract

The unc-4 gene of Caenorhabditis elegans encodes a homeodomain protein that defines synaptic input to ventral cord motor neurons. unc-4 mutants are unable to crawl backward because VA motor neurons are miswired with synaptic connections normally reserved for their sister cells, the VB motor neurons. These changes in connectivity are not accompanied by any visible effects upon neuronal morphology, which suggests that unc-4 regulates synaptic specificity but not axonal guidance or outgrowth. In an effort to identify other genes in the unc-4 pathway, we have devised a selection scheme for rare mutations that suppress the Unc-4 phenotype. We have isolated four, dominant, extragenic, allele-specific suppressors of unc-4(e2322ts), a temperature sensitive allele with a point mutation in the unc-4 homeodomain. Our data indicate that these suppressors are gain-of-function mutations in the previously identified unc-37 gene. We show that the loss-of-function mutation unc-37(e262) phenocopies the Unc-4 movement defect but does not prevent unc-4 expression or alter VA motor neuron morphology. These findings suggest that unc-37 functions with unc-4 to specify synaptic input to the VA motor neurons. We propose that unc-37 may be regulated by unc-4. Alternatively, unc-37 may encode a gene product that interacts with the unc-4 homeodomain.

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Selected References

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  • Botstein D, Maurer R. Genetic approaches to the analysis of microbial development. Annu Rev Genet. 1982;16:61–83. [PubMed]
  • Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. [PMC free article] [PubMed]
  • Chalfie M, Sulston JE, White JG, Southgate E, Thomson JN, Brenner S. The neural circuit for touch sensitivity in Caenorhabditis elegans. J Neurosci. 1985 Apr;5(4):956–964. [PubMed]
  • Clark SG, Stern MJ, Horvitz HR. C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains. Nature. 1992 Mar 26;356(6367):340–344. [PubMed]
  • Coulson A, Waterston R, Kiff J, Sulston J, Kohara Y. Genome linking with yeast artificial chromosomes. Nature. 1988 Sep 8;335(6186):184–186. [PubMed]
  • Finney M, Ruvkun G, Horvitz HR. The C. elegans cell lineage and differentiation gene unc-86 encodes a protein with a homeodomain and extended similarity to transcription factors. Cell. 1988 Dec 2;55(5):757–769. [PubMed]
  • Gilchrist EJ, Moerman DG. Mutations in the sup-38 gene of Caenorhabditis elegans suppress muscle-attachment defects in unc-52 mutants. Genetics. 1992 Oct;132(2):431–442. [PMC free article] [PubMed]
  • Goodman CS, Shatz CJ. Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell. 1993 Jan;72 (Suppl):77–98. [PubMed]
  • Greenwald IS, Horvitz HR. unc-93(e1500): A behavioral mutant of Caenorhabditis elegans that defines a gene with a wild-type null phenotype. Genetics. 1980 Sep;96(1):147–164. [PMC free article] [PubMed]
  • Hengartner MO, Ellis RE, Horvitz HR. Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature. 1992 Apr 9;356(6369):494–499. [PubMed]
  • Jessell TM, Kandel ER. Synaptic transmission: a bidirectional and self-modifiable form of cell-cell communication. Cell. 1993 Jan;72 (Suppl):1–30. [PubMed]
  • Leung-Hagesteijn C, Spence AM, Stern BD, Zhou Y, Su MW, Hedgecock EM, Culotti JG. UNC-5, a transmembrane protein with immunoglobulin and thrombospondin type 1 domains, guides cell and pioneer axon migrations in C. elegans. Cell. 1992 Oct 16;71(2):289–299. [PubMed]
  • Li W, Herman RK, Shaw JE. Analysis of the Caenorhabditis elegans axonal guidance and outgrowth gene unc-33. Genetics. 1992 Nov;132(3):675–689. [PMC free article] [PubMed]
  • Lieber T, Wesley CS, Alcamo E, Hassel B, Krane JF, Campos-Ortega JA, Young MW. Single amino acid substitutions in EGF-like elements of Notch and Delta modify Drosophila development and affect cell adhesion in vitro. Neuron. 1992 Nov;9(5):847–859. [PubMed]
  • Maruyama IN, Miller DM, Brenner S. Myosin heavy chain gene amplification as a suppressor mutation in Caenorhabditis elegans. Mol Gen Genet. 1989 Oct;219(1-2):113–118. [PubMed]
  • McKim KS, Starr T, Rose AM. Genetic and molecular analysis of the dpy-14 region in Caenorhabditis elegans. Mol Gen Genet. 1992 May;233(1-2):241–251. [PubMed]
  • Miller DM, Shen MM, Shamu CE, Bürglin TR, Ruvkun G, Dubois ML, Ghee M, Wilson L. C. elegans unc-4 gene encodes a homeodomain protein that determines the pattern of synaptic input to specific motor neurons. Nature. 1992 Feb 27;355(6363):841–845. [PubMed]
  • Miller LM, Plenefisch JD, Casson LP, Meyer BJ. xol-1: a gene that controls the male modes of both sex determination and X chromosome dosage compensation in C. elegans. Cell. 1988 Oct 7;55(1):167–183. [PubMed]
  • Qian YQ, Billeter M, Otting G, Müller M, Gehring WJ, Wüthrich K. The structure of the Antennapedia homeodomain determined by NMR spectroscopy in solution: comparison with prokaryotic repressors. Cell. 1989 Nov 3;59(3):573–580. [PubMed]
  • Rebay I, Fleming RJ, Fehon RG, Cherbas L, Cherbas P, Artavanis-Tsakonas S. Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell. 1991 Nov 15;67(4):687–699. [PubMed]
  • Rogge RD, Karlovich CA, Banerjee U. Genetic dissection of a neurodevelopmental pathway: Son of sevenless functions downstream of the sevenless and EGF receptor tyrosine kinases. Cell. 1991 Jan 11;64(1):39–48. [PubMed]
  • Rose AM, Baillie DL. Genetic organization of the region around UNC-15 (I), a gene affecting paramyosin in Caenorhabditis elegans. Genetics. 1980 Nov;96(3):639–648. [PMC free article] [PubMed]
  • Schier AF, Gehring WJ. Direct homeodomain-DNA interaction in the autoregulation of the fushi tarazu gene. Nature. 1992 Apr 30;356(6372):804–807. [PubMed]
  • Stern S, Herr W. The herpes simplex virus trans-activator VP16 recognizes the Oct-1 homeo domain: evidence for a homeo domain recognition subdomain. Genes Dev. 1991 Dec;5(12B):2555–2566. [PubMed]
  • Ward S. Chemotaxis by the nematode Caenorhabditis elegans: identification of attractants and analysis of the response by use of mutants. Proc Natl Acad Sci U S A. 1973 Mar;70(3):817–821. [PMC free article] [PubMed]
  • Waterston RH, Fishpool RM, Brenner S. Mutants affecting paramyosin in Caenorhabditis elegans. J Mol Biol. 1977 Dec 15;117(3):679–697. [PubMed]
  • Waterston RH, Thomson JN, Brenner S. Mutants with altered muscle structure of Caenorhabditis elegans. Dev Biol. 1980 Jun 15;77(2):271–302. [PubMed]
  • Way JC, Wang L, Run JQ, Wang A. The mec-3 gene contains cis-acting elements mediating positive and negative regulation in cells produced by asymmetric cell division in Caenorhabditis elegans. Genes Dev. 1991 Dec;5(12A):2199–2211. [PubMed]
  • White JG, Southgate E, Thomson JN. Mutations in the Caenorhabditis elegans unc-4 gene alter the synaptic input to ventral cord motor neurons. Nature. 1992 Feb 27;355(6363):838–841. [PubMed]

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