THE C-ELEGANS GENE PAG-3 IS HOMOLOGOUS TO THE ZINC-FINGER PROTOONCOGENE GFI-1

Mutations in the Caenorhabditis elegans gene pag-3 result in misexpres sion of touch receptor-specific genes in the BDU interneurons and in m otility defects, We cloned pag-3 and found that the gene encodes a C2H 2-type zinc finger protein related to the mammalian GFI-1 protein. Seq uencing of the three pag-3 alleles showed that two apparent null allel es encode a nonsense mutation before the zinc fingers and a missense m utation in the fourth zinc finger that changes a coordinating histidin e to a tyrosine. The third allele contains a nonsense mutation in the N-terminal region but is not a null allele. Northern analysis showed t hat a single pag-3 transcript of about 1.6 kb is present in embryos an d L1, L2 and L3 larvae, pag-3 message levels were about twofold higher in pag-3 mutants than in wild-type animals, which suggested that pag- 3 may negatively regulate its own expression, pag-3lacZ fusion genes w ere expressed in the BDU interneurons, the touch neurons, 11 VA and 11 VB ventral cord motor neurons, two AVF interneurons and in unidentifi ed neurons of the retrovesicular ganglion, The BDU neurons and the ALM touch neurons are lineal sister cells in the AB.a lineage and the VA and VB motor neurons are lineal sister cells in the AB.p lineage. The VA motor neurons are required for backward movement and the VB motor n eurons are required for forward movement, Mosaic analysis showed that the wildtype pag-3 gene is required in the AB.p lineage for coordinate d movement and in the AB.a lineage to suppress touch neuron gene expre ssion in the BDU neurons. Because pag-3 is expressed in both the BDU n eurons and in the touch neurons, another protein(s) not expressed in t he touch neurons may interact with pag-3 to repress touch neuron gene expression in the BDU neurons, Alternatively, another protein in the t ouch receptor cells may inactivate PAG-3 and allow expression of the t ouch receptor program, These results show that pag-3 is a temporally r egulated gene that is expressed early in development and functions in multiple types of neurons, They also strongly suggest that the PAG-3 p rotein is a DNA-binding protein with properties similar to the mammali an proto-oncogene product GFI-1.