Genetics, Vol 135, 741-753, Copyright © 1993

INVESTIGATIONS

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

D. M. Miller-III, C. J. Niemeyer and P. Chitkara
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710-3011

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.

This article has been cited by other articles:

				S. Sarin, M. M. O'Meara, E. B. Flowers, C. Antonio, R. J. Poole, D. Didiano, R. J. Johnston Jr., S. Chang, S. Narula, and O. Hobert Genetic Screens for Caenorhabditis elegans Mutants Defective in Left/Right Asymmetric Neuronal Fate Specification Genetics, August 1, 2007; 176(4): 2109 - 2130. [Abstract] [Full Text] [PDF]

				S. Znaidi, B. Pelletier, Y. Mukai, and S. Labbe The Schizosaccharomyces pombe Corepressor Tup11 Interacts with the Iron-responsive Transcription Factor Fep1 J. Biol. Chem., March 5, 2004; 279(10): 9462 - 9474. [Abstract] [Full Text] [PDF]

				B. Esmaeili, J. M. Ross, C. Neades, D. M. Miller III, and J. Ahringer The C. elegans even-skipped homologue, vab-7, specifies DB motoneurone identity and axon trajectory Development, March 4, 2003; 129(4): 853 - 862. [Abstract] [Full Text] [PDF]

				K. M. Lickteig, J. S. Duerr, D. L. Frisby, D. H. Hall, J. B. Rand, and D. M. Miller III Regulation of Neurotransmitter Vesicles by the Homeodomain Protein UNC-4 and Its Transcriptional Corepressor UNC-37/Groucho in Caenorhabditis elegans Cholinergic Motor Neurons J. Neurosci., March 15, 2001; 21(6): 2001 - 2014. [Abstract] [Full Text] [PDF]

				A. R. Winnier, J. Y.-J. Meir, J. M. Ross, N. Tavernarakis, M. Driscoll, T. Ishihara, I. Katsura, and D. M. Miller III UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans Genes & Dev., November 1, 1999; 13(21): 2774 - 2786. [Abstract] [Full Text]

				L. Bloom and H. R. Horvitz The Caenorhabditis elegans gene unc-76 and its human homologs define a new gene family involved in axonal outgrowth and fasciculation PNAS, April 1, 1997; 94(7): 3414 - 3419. [Abstract] [Full Text] [PDF]

				A Pflugrad, J. Meir, T. Barnes, and D. Miller The Groucho-like transcription factor UNC-37 functions with the neural specificity gene unc-4 to govern motor neuron identity in C. elegans Development, January 5, 1997; 124(9): 1699 - 1709. [Abstract] [PDF]

				D. Miller and C. Niemeyer Expression of the unc-4 homeoprotein in Caenorhabditis elegans motor neurons specifies presynaptic input Development, January 9, 1995; 121(9): 2877 - 2886. [Abstract] [PDF]