Cell fates and fusion in theC. elegansvulval primordium are regulated by the EGL-18 and ELT-6 GATA factors — apparent direct targets of the LIN-39 Hox protein

• DOI: 10.1242/dev.129.22.5171
• Publication Date: 2021-04-26T14:50:09Z
• Authors: Kyunghee Koh; Sara M. Peyrot; Cricket G. Wood; Javier A. Wagmaister; Morris F. Maduro; David M. Eisenmann; Joel H. Rothman
• Keywords: Homeodomain Proteins; Neurons; 0303 health sciences; Binding Sites; Green Fluorescent Proteins; Cell Differentiation; Helminth Proteins; GATA Transcription Factors; Recombinant Proteins; Vulva; Cell Fusion; DNA-Binding Proteins; Luminescent Proteins; 03 medical and health sciences; Enhancer Elements, Genetic; Mutation; Animals; Female; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Dimerization; Transcription Factors

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 thelin-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-6reporter gene expression in the developing vulva is attenuated inlin-39(rf) mutants, and overexpression of egl-18 can partially rescue the vulval defects caused by reduced lin-39activity. 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.