Pax-6 is a transcription factor containing two conserved DNA binding domains, the paired and the homeo domains. Pax-6 is required in the development of eye and CNS in metazoa. C. elegans Pax-6 encodes two transcription units corresponding to two genetic loci,
vab-3 (1) and
mab-18 (2).
vab-3 transcripts have both the paired and the homeo domains.
mab-18 transcripts have only the C-terminal portion containing the homeodomain, together with
mab-18-specific N-terminal exons. Paired-less
mab-18 transcripts are transcribed from an internal promoter located in a region between the paired and homeodomain containing exons.
vab-3 is required in the patterning of the head region.
mab-18 is required to specify the identity of one pair of sensory rays (ray 6) in the male tail. Expression pattern studies using
mab-18 lacZ and GFP reporters suggested that
mab-18 is specifically expressed in ray 6 and ray 8 and in a few neurons in the preanal ganglion (2). We wonder how
mab-18 is specifically turned on in these cells. By studying the expression of
mab-18 reporters in different mutant backgrounds, we found
mab-18 expression is regulated by two genes in the HOX cluster,
egl-5 and
mab-5, and by genes in the TGF-b signal transduction pathway. In addition, an important component appears to be a positive autoregulation by
mab-18, since the reporters were not expressed in the preanal ganglion or in ray 6 in
mab-18 mutants.
mab-5 and
egl-5 appear to act differently in the regulation of
mab-18 expression.
mab-5 is required for
mab-18 expression in the preanal ganglion. In contrast,
egl-5 appears to inhibit
mab-18 expression in P12 derived cells in the preanal ganglion. This inhibition appears to be achieved through blocking
mab-5 activity. In an
egl-5 mab-5 double mutant, expression of the
mab-18 reporter in the preanal ganglion was abolished.
daf-4,
sma-2,
sma-3, and
sma-4 are genes encoding proteins in the TGF-beta signal transduction pathway (3, 4). Mutations in these genestransform other rays to fat rays like ray 6 (4, 5). These transformations appear to be a result of
mab-18 expression in these rays. Consistent with this interpretation,
mab-18 reporters are expressed in extra ray cells in the tail of these mutants. Thus, in wild type, the TGF-beta signal transduction pathway inhibits
mab-18 expression in some rays other than ray 6. In summary, this study suggests expression of
mab-18 is regulated by different mechanisms in different cells. It appears that a combinatorial action of these cell autonomous and non-autonomous genes restrict
mab-18 function to a small number of cells. Ref. (1). Chisholm and Horvitz (1995). Nature 377, 52. (2) Zhang and Emmons (1995). Nature 377, 55. (3) Estevez et al. (1993), Nature 365, 644. (4) Savage et al. (1996). (submitted). (5) Baird et al. (1991). Develop. 113, 515.