gon-2 encodes a TRPM family cation channel that is required for the initiation of postembryonic divisions by the gonadal precursor cells. The roles and regulation of TRPM channels during metazoan development are not well understood.<span style="mso-spacerun: yes"> </span>In order to identify extragenic regulatory loci, we conducted a large scale reversion screen of the temperature sensitive allele,
gon-2(
q388ts)</span><span style='font-size:14.0pt'>. <span style='color:black'>We screened approximately 1,500,000 mutagenized genomes and identified 31 suppressor mutations.<span style="mso-spacerun: yes"> </span>Seven of these are on chromosome I, and are likely to be intragenic revertants. Fourteen of the remaining 24 mutations are both sex-linked and dominant, </span>so we tentatively assigned these to a single locus,
gem-1</span><span style='font-size:14.0pt'>(
gon-2</span><span style='font-size:14.0pt'> extragenic modifier). Suppression by
gem-1</span><span style='font-size:14.0pt'> is not allele-specific and even occurs with putative null alleles of
gon-2.Through a combination of SNP mapping and RNAi, we determined that
gem-1</span><span style='font-size:14.0pt'> encodes a predicted multipass transmembrane protein of the solute transporter superfamily. Although the high frequency of allele isolation would suggest that the suppressor mutations are probably loss-of-function alleles, three lines of evidence indicate that these are actually gain-of-function mutations.<span style="mso-spacerun: yes"> </span>First, each of the 14 different alleles results in a single amino acid change; none are obviously loss-of-function mutations.<span style="mso-spacerun: yes"> </span>Second,
gem-1(RNAi)</span><span style='font-size:14.0pt'> abolishes suppression by the suppressor alleles of
gem-1</span><span style='font-size:14.0pt'>.<span style="mso-spacerun: yes"> </span>Finally, the knockout allele,
gem-1(
bc364)</span><span style='font-size:14.0pt'> (generously provided by Barbara Conradt), is recessive and enhances, rather than suppresses,
gon-2(
q388ts)</span><span style='font-size:14.0pt'>. Our current hypothesis is that
gem-1(+)</span><span style='font-size:14.0pt'> ordinarily operates in parallel to
gon-2(+)</span><span style='font-size:14.0pt'> to mediate cation uptake by the gonadal precursors. The suppressor alleles increase the effective activity of
gem-1</span><span style='font-size:14.0pt'>, either by altering the specificity of the transporter or by increasing its overall level of activity. <o:p></o:p></span> <p class=MsoNormal><span style='font-size:14.0pt'><![if !supportEmptyParas]><![endif]><o:p></o:p></span>