title: 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.
abstract: 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. LIN-39 specifies cell fates and regulates cell fusion in the mid-body region, leading to formation of the vulva. In the lateral seam epidermis, differentiation and cell fusion have been shown to be regulated by two GATA-type transcription factors, ELT-5 and -6. We report that ELT-5 is encoded by the egl-18 gene, which was previously shown to promote formation of a functional vulva. Furthermore, we find that EGL-18 (ELT-5), and its paralogue ELT-6, are redundantly required to regulate cell fates and fusion in the vulval primordium and are essential to form a vulva. Elimination of egl-18 and elt-6 activity results in arrest by the first larval stage; however, in animals rescued for this larval lethality by expression of ELT-6 in non-vulval cells, the post-embryonic cells (P3.p-P8.p) that normally become vulval precursor cells often fuse with the surrounding epidermal syncytium or undergo fewer than normal cell divisions, reminiscent of lin-39 mutants. Moreover, egl-18/elt-6 reporter gene expression in the developing vulva is attenuated in lin-39(rf) mutants, and overexpression of egl-18 can partially rescue the vulval defects caused by reduced lin-39 activity. LIN-39/CEH-20 heterodimers bind two consensus HOX/PBC sites in a vulval enhancer region of egl-18/elt-6, one of which is essential for vulval expression of egl-18/elt-6 reporter constructs. These findings demonstrate that the EGL-18 and ELT-6 GATA factors are essential, genetically redundant regulators of cell fates and fusion in the developing vulva and are apparent direct transcriptional targets of the LIN-39 Hox protein.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Koh
authors.forename: Sara M
authors.initials: SM
authors.lastname: Peyrot
authors.forename: Cricket G
authors.initials: CG
authors.lastname: Wood
authors.forename: Javier A
authors.initials: JA
authors.lastname: Wagmaister
authors.forename: Morris F
authors.initials: MF
authors.lastname: Maduro
authors.forename: David M
authors.initials: DM
authors.lastname: Eisenmann
authors.forename: Joel H
authors.initials: JH
authors.lastname: Rothman
mesh_terms: D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002459:Cell Fusion; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D004742:Enhancer Elements, Genetic; D005260:Female; D050980:GATA Transcription Factors; D049452:Green Fluorescent Proteins; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014844:Vulva / Q000002:abnormalities / Q000254:growth & development* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D050980:GATA Transcription Factors; D015801:Helminth Proteins; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C418523:ceh-20 protein, C elegans; C434745:egl-18 protein, C elegans; C434746:elt-6 protein, C elegans; C108673:lin-39 protein, C elegans; D049452:Green Fluorescent Proteins