The A-type motor neurons, DA and VA, receive input from specific interneurons that drive backward movement. The B-type motor neurons, DB and VB, are connected to a separate set of interneurons that activate forward movement. The creation of these discrete motor neuron types and circuits is required for normal locomotion. The UNC-4 homeodomain protein is expressed in A-type motor neurons (DA, VA) but not in B-type motor neurons (DB, VB). Ectopic expression of UNC-4 in VB motor neurons produces a strong uncoordinated phenotype that may result from the miswiring of VBs with VA-type inputs (J. Ross, this meeting). This result suggested to us that it may be functionally important to prevent
unc-4 expression in B-type motor neurons. Here we show that
unc-4 is negatively regulated in DB and VB motor neurons by two different transcription factors: the Eve homeoprotein,VAB-7, blocks
unc-4 expression in the DBs and the Olf-1/EBF (O/E) zinc-finger protein, UNC-3, represses
unc-4 in the VBs. DA and DB motor neurons arise embryonically in the ventral nerve cord and extend commissures to innervate dorsal muscles.
vab-7 is selectively expressed in the DBs (2). In
vab-7(
e1562),
unc-4::gfp is expressed in both DAs and DBs. Conversely, the
vab-7 mutation quenches
acr-5::gfp expression in the DBs. We have previously shown that
acr-5::gfp is normally expressed in B-type motor neurons and is negatively regulated by
unc-4 in A-type motor neurons (1). Thus, the elimination of
acr-5::gfp expression in the DBs in
vab-7(
e1562), is consistent with de-repression of the endogenous
unc-4 gene in the DBs. That this loss of
acr-5::gfp expression in the DBs depends on UNC-4 is also supported by our finding that
acr-5::gfp expression is restored to the DBs in
vab-7;
unc-4 mutants. Thus, our results are indicative of genetic pathway in which
vab-7 negatively regulates
unc-4 which negatively regulates
acr-5 in DB motor neurons. It will be interesting to determine if the forward movement defect that
vab-7 mutants display (2) depends on ectopic
unc-4 expression in the DBs. VA and VB sister cells arise in the late L1 and send out processes to innervate ventral muscles. UNC-3 is normally expressed in all A-type and B-type motor neurons (3,4). In
unc-3(
e151),
unc-4::gfp is ectopically expressed in the VBs in addition to its normal expression in the VAs.
acr-5::gfp is also extinguished in the VBs which is consistent with the de-repression of
unc-4. We conclude that UNC-3 is a negative regulator of
unc-4 in the VBs. Curiously, UNC-3 does not repress
unc-4 in the VAs although UNC-3 is normally expressed in these cells. In addition,
unc-3 function appears to activate
unc-4::gfp expression in DA motor neurons. Thus, the regulation of
unc-4 by
unc-3 is complex and may be positive, negative or neutral in different neurons. The negative regulation of
unc-4 in VB motor neurons predicts that VB motor neurons will assume VA-like traits in
unc-3 mutants. Perhaps the apparent reversal of axonal polarity that has been reported for VB motor neurons in
unc-3 mutants (J. White, personal communication) depends on ectopic UNC-4 expression in these cells. 1. Ross, J., et al. 1997 C. elegans Meeting 2. B. Esmaeili, C. Neades, J. Ahringer. 1997 International C. elegans Meeting 3. T. Starich, S. Eddy, R. K. Herman, and J. Shaw, personal communication. 4. Prasad, B. C., et al. (1998) Development 125, 1561-1568.