UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans.
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.
Winnier
A R
AR
Department of Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Meir
J Y
JY
Ross
J M
JM
Tavernarakis
N
N
Driscoll
M
M
Ishihara
T
T
Katsura
I
I
Miller
D M
DM
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D018398:Homeodomain Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C106184:unc-37 protein, C elegans; C073171:unc-4 protein, C elegans