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Vol. 13, No. 21, pp. 2774-2786, November 1, 1999
1 Department of Cell Biology, Vanderbilt University Medical
Center, Nashville, Tennessee 37232 USA; 2 Department of
Molecular Biology and Biochemistry, Rutgers University, New Brunswick,
New Jersey 08855 USA; 3 National Institute of Genetics,
Mishima, Japan
The UNC-4 homeoprotein and the Groucho-like corepressor UNC-37
specify synaptic choice in the Caenorhabditis elegans motor neuron circuit. In unc-4 mutants, VA motor neurons are miswired with inputs from interneurons normally reserved for their lineal sisters, the VB motor neurons. Here we show that UNC-4 and UNC-37 function together in VA motor neurons to repress VB-specific genes and
that this activity depends on physical contact between UNC-37 and a
conserved Engrailed-like repressor domain (eh1) in UNC-4. Missense
mutations in the UNC-4 eh1 domain disrupt interactions between UNC-4
and UNC-37 and result in the loss of UNC-4-dependent repressor activity
in vivo. A compensatory amino acid substitution in UNC-37 suppresses
specific unc-4 alleles by restoring physical interactions with
UNC-4 as well as UNC-4-dependent repression of VB-specific genes. We
propose that repression of VB-specific genes by UNC-4 and UNC-37 is
necessary for the creation of wild-type inputs to VA motor neurons. The
existence of mammalian homologs of UNC-4 and UNC-37 indicates that a
similar mechanism could regulate synaptic choice in the vertebrate
spinal cord.
[Key Words: Groucho; unc-4; repression; C. elegans; synaptic specificity]
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