High impact information on lin-39

• Control of cell fates in the central body region of C. elegans by the homeobox gene lin-39 [1].
• In Caenorhabditis, lin-39 prevents cell fusion of potential vulval cells and specifies the vulva equivalence group [2].
• Pristionchus vulvaless mutants that displayed apoptosis of the vulval precursor cells were isolated, and point mutations in lin-39 were identified [2].
• The homeotic gene lin-39 and the evolution of nematode epidermal cell fates [2].
• The Overinduced phenotype is suppressed by reduction of function of the genes pop-1 TCF and lin-39 Hox [3].

Biological context of lin-39

• A single binding site for the ETS factor LIN-1 mediates repression in VPCs other than P6.p; however, loss of LIN-1 decreases expression in P6.p. Therefore, LIN-1 acts both negatively and positively on lin-39 in different VPCs [4].
• Finally, LIN-39 itself binds to this element, suggesting that LIN-39 autoregulates its expression in P6.p. Therefore, we have begun to unravel the cis-acting sites regulating lin-39 Hox gene expression and have shown that lin-39 is a direct target of the Ras pathway acting via LIN-1 and LIN-31 [4].
• In a subset of Pn.p cells, called vulval precursor cells, nhr-25 acts collaboratively with the lin-39 Hox gene in regulating vulval cell differentiation [5].
• In C. elegans, two Hox genes, lin-39 and mab-5, control the cell fusion decision of the 12 ventrally located Pn.p cells [6].
• Our findings suggest that in addition to permitting vulval cell divisions to occur, lin-39 is also required to specify the outcome of Ras signaling by selectively activating vulva-specific genes [7].

Anatomical context of lin-39

• Development of the vulva in C. elegans is mediated by the combinatorial action of several convergent regulatory inputs, three of which, the Ras, Wnt and Rb-related pathways, act by regulating expression of the lin-39 Hox gene [8].
• By examining the M lineage and its differentiation products in different Hox mutant combinations, we found an essential but overlapping role for two of the Hox cluster genes, lin-39 and mab-5, in diversification of the postembryonic mesoderm [9].
• C. elegans lin-39 mutants are vulvaless and the vulval precursor cells fuse with the surrounding hypodermis, whereas in P. pacificus lin-39 mutants the vulval precursor cells die by apoptosis [10].
• In this group, we found a putative null mutation in the lin-39 HOM-C homolog, the associated phenotype of which could be weakly mimicked by injection of a morpholino against Osp1-lin-39 in the mother's germ line [11].

Regulatory relationships of lin-39

• The beta-catenin homolog BAR-1 and LET-60 Ras coordinately regulate the Hox gene lin-39 during Caenorhabditis elegans vulval development [12].
• sem-4 promotes vulval cell-fate determination in Caenorhabditis elegans through regulation of lin-39 Hox [13].

Other interactions of lin-39

• Thus, in this process, too, ceh-20 and unc-62 are likely to have functions that are independent of lin-39 [14].
• Surprisingly, ceh-20 and unc-62 mutants have phenotypes that are starkly different from those of lin-39 mutants [14].
• For example, neurons are specified along the anterior-posterior body axis through the action of the Hox genes lin-39, mab-5, and egl-5 [15].
• We find that the pattern of fates specified by mab-5 not only depends on mab-5 expression but also on post-translational interactions with the neighboring HOM-C gene lin-39 and a second, inferred gene activity [16].
• To study the mechanism of lin-39 function, we isolated P. pacificus cell death mutants and identified mutations in ced-3 [10].

Analytical, diagnostic and therapeutic context of lin-39

• Here, we study evolutionary changes of lin-39 function using hybrid transgenes and site-directed mutagenesis in an in vivo assay using C. elegans lin-39 mutants [17].

References