Worm Breeder's Gazette 14(3): 36 (June 1, 1996)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Regulation of the expression of a C. elegans Pax-6 homolog, mab-18, by HOX genes and TGF-b signaling

Yinhua Zhang, Scott W. Emmons

Dept. Molecular of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Av., Bronx, NY 10461

        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-b signal transduction pathway (3, 4).  Mutations in these genes
transform 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-b 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.