Worm Breeder's Gazette 11(3): 28

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.

The Cloning and Preliminary Molecular Characterization of sdc-1

Michael L. Nonet and Barbara J. Meyer

The X-linked sdc-1 gene is required for the hermaphrodite mode of 
sex determination and dosage compensation, acting at a point before 
the two pathways diverge.  Temperature-shift experiments further 
suggest that sdc-1 acts at an early step in the regulatory hierarchy 
controlling the choice of sexual fate since they demonstrate a 
requirement for sdc-1 during the first half of embryogenesis (
Villeneuve and Meyer, Genetics 124:91-114, 1990).  We have undertaken 
a molecular approach to examine the function of this gene in the sex 
determination and dosage compensation processes in C.  elegans.  Here 
we describe the cloning and preliminary molecular examination of this 
locus.
The sdc-1 gene was positioned to a two cosmid interval on the clb-1 
contig by identifying the breakpoints of two deficiencies that flank 
the gene, the left breakpoint of mnDf41 (in R09G6) and the right 
breakpoint of mnDf4 (in R12G12).  Restriction mapping of the 
overlapping R12G12, W06F3 and R09G6 cosmids in conjunction with 
further molecular characterization of the mnDf41 and mnDf8 breakpoints 
localized sdc-1 to a 55 kb interval.
Micro-injection rescue of sdc-1(y67) with cosmids and cosmid 
subclones in this interval localized sdc-1 rescuing activity to an 11 
kb fragment within R09G6.  Rescuing clones completely eliminate the 
sdc-1 Tra, Egl and Dpy mutant phenotypes in the F1 and in subsequent 
generations.  Concerned that duplications of portions of the X 
chromosome that do not cover sdc-1 suppress the sdc-1 phenotype, we 
were relieved that neither adjacent cosmids nor act-4 subclones, which 
contain a feminizing element defined by McCoubrey et al.  (Science 
242:1146-51, 1988), are able to rescue sdc-1.   [Interestingly, we 
further noticed that neither of two act-4 clones we utilized will 
produce stable transmitting lines in co-injections with rol-6(su1006), 
although F1 roller transformed animals are easily obtainable.
]
To analyze sdc-1 transcripts, an overlapping set of fragments 
spanning the 11 kb rescuing region were subcloned and used to probe 
Northern blots loaded with 20 g of polyA+ RNA isolated from mixed 
staged cultures of both N2 and him-8 strains.  A 'single' smeary ~3.8 
kb transcript derives from the middle 6 kb region of our rescuing 
fragment.  Southern analysis of 14 sdc-1 alleles (13 EMS induced, 1 
spontaneous) using these same probes showed no obvious allele-specific 
polymorphisms in the region.
We are in the process of isolating cDNA clones from the region from 
both him-5 and N2 cDNA libraries, and are determining the genomic 
sequence of the locus.  The molecular analysis of this gene in 
conjunction with concurrent analysis of the sdc-2, 
uld expand our understanding of 
the early steps of both the sex determination and dosage compensation 
pathways in C.  elegans.