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Gene Review

lin-39  -  Protein LIN-39

Caenorhabditis elegans

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High impact information on lin-39


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


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


  1. Control of cell fates in the central body region of C. elegans by the homeobox gene lin-39. Clark, S.G., Chisholm, A.D., Horvitz, H.R. Cell (1993) [Pubmed]
  2. The homeotic gene lin-39 and the evolution of nematode epidermal cell fates. Eizinger, A., Sommer, R.J. Science (1997) [Pubmed]
  3. Activation of Wnt signaling bypasses the requirement for RTK/Ras signaling during C. elegans vulval induction. Gleason, J.E., Korswagen, H.C., Eisenmann, D.M. Genes Dev. (2002) [Pubmed]
  4. Identification of cis-regulatory elements from the C. elegans Hox gene lin-39 required for embryonic expression and for regulation by the transcription factors LIN-1, LIN-31 and LIN-39. Wagmaister, J.A., Miley, G.R., Morris, C.A., Gleason, J.E., Miller, L.M., Kornfeld, K., Eisenmann, D.M. Dev. Biol. (2006) [Pubmed]
  5. The Caenorhabditis elegans nuclear receptor gene nhr-25 regulates epidermal cell development. Chen, Z., Eastburn, D.J., Han, M. Mol. Cell. Biol. (2004) [Pubmed]
  6. REF-1, a protein with two bHLH domains, alters the pattern of cell fusion in C. elegans by regulating Hox protein activity. Alper, S., Kenyon, C. Development (2001) [Pubmed]
  7. The Hox gene lin-39 is required during C. elegans vulval induction to select the outcome of Ras signaling. Maloof, J.N., Kenyon, C. Development (1998) [Pubmed]
  8. Cell fates and fusion in the C. elegans vulval primordium are regulated by the EGL-18 and ELT-6 GATA factors -- apparent direct targets of the LIN-39 Hox protein. Koh, K., Peyrot, S.M., Wood, C.G., Wagmaister, J.A., Maduro, M.F., Eisenmann, D.M., Rothman, J.H. Development (2002) [Pubmed]
  9. Overlapping roles of two Hox genes and the exd ortholog ceh-20 in diversification of the C. elegans postembryonic mesoderm. Liu, J., Fire, A. Development (2000) [Pubmed]
  10. The Pristionchus HOX gene Ppa-lin-39 inhibits programmed cell death to specify the vulva equivalence group and is not required during vulval induction. Sommer, R.J., Eizinger, A., Lee, K.Z., Jungblut, B., Bubeck, A., Schlak, I. Development (1998) [Pubmed]
  11. Control of vulval competence and centering in the nematode Oscheius sp. 1 CEW1. Louvet-Vallée, S., Kolotuev, I., Podbilewicz, B., Félix, M.A. Genetics (2003) [Pubmed]
  12. The beta-catenin homolog BAR-1 and LET-60 Ras coordinately regulate the Hox gene lin-39 during Caenorhabditis elegans vulval development. Eisenmann, D.M., Maloof, J.N., Simske, J.S., Kenyon, C., Kim, S.K. Development (1998) [Pubmed]
  13. sem-4 promotes vulval cell-fate determination in Caenorhabditis elegans through regulation of lin-39 Hox. Grant, K., Hanna-Rose, W., Han, M. Dev. Biol. (2000) [Pubmed]
  14. The roles of two C. elegans HOX co-factor orthologs in cell migration and vulva development. Yang, L., Sym, M., Kenyon, C. Development (2005) [Pubmed]
  15. Cell fate specification and differentiation in the nervous system of Caenorhabditis elegans. Sengupta, P., Bargmann, C.I. Dev. Genet. (1996) [Pubmed]
  16. Multiple HOM-C gene interactions specify cell fates in the nematode central nervous system. Salser, S.J., Loer, C.M., Kenyon, C. Genes Dev. (1993) [Pubmed]
  17. Functional comparison of the nematode Hox gene lin-39 in C. elegans and P. pacificus reveals evolutionary conservation of protein function despite divergence of primary sequences. Grandien, K., Sommer, R.J. Genes Dev. (2001) [Pubmed]
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