Fernandes, Jolene S. and Sternberg, Paul W. (2007) The tailless Ortholog nhr-67 Regulates Patterning of Gene Expression and Morphogenesis in the C. elegans Vulva. PLoS Genetics, 3 (4). pp. 603-616. ISSN 1553-7390 http://resolver.caltech.edu/CaltechAUTHORS:FERplosg07
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Regulation of spatio-temporal gene expression in diverse cell and tissue types is a critical aspect of development. Progression through Caenorhabditis elegans vulval development leads to the generation of seven distinct vulval cell types (vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF), each with its own unique gene expression profile. The mechanisms that establish the precise spatial patterning of these mature cell types are largely unknown. Dissection of the gene regulatory networks involved in vulval patterning and differentiation would help us understand how cells generate a spatially defined pattern of cell fates during organogenesis. We disrupted the activity of 508 transcription factors via RNAi and assayed the expression of ceh-2, a marker for vulB fate during the L4 stage. From this screen, we identified the tailless ortholog nhr-67 as a novel regulator of gene expression in multiple vulval cell types. We find that one way in which nhr-67 maintains cell identity is by restricting inappropriate cell fusion events in specific vulval cells, namely vulE and vulF. nhr-67 exhibits a dynamic expression pattern in the vulval cells and interacts with three other transcriptional regulators cog-1 (Nkx6.1/6.2), lin-11 (LIM), and egl-38 (Pax2/5/8) to generate the composite expression patterns of their downstream targets. We provide evidence that egl-38 regulates gene expression in vulB1, vulC, vulD, vulE, as well as vulF cells. We demonstrate that the pairwise interactions between these regulatory genes are complex and vary among the seven cell types. We also discovered a striking regulatory circuit that affects a subset of the vulval lineages: cog-1 and nhr-67 inhibit both one another and themselves. We postulate that the differential levels and combinatorial patterns of lin-11, cog-1, and nhr-67 expression are a part of a regulatory code for the mature vulval cell types.
|Additional Information:||© 2007 Fernandes and Sternberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: December 1, 2006; Accepted: March 16, 2007; Published: April 27, 2007. We thank Minqin Wang for strain constructions; Helen Chamberlin for the guEx64 strain; the Fire lab for GFP vectors; Nathalie Pujol for the pNP10 plasmid; and Andrew Udit, Mihoko Kato, Gladys Medina, and Barbara Perry for technical assistance. The nhr-67 deletion allele (ok631) and kuIs36 was provided by the C. elegans Genetic Center. We also thank Elissa Hallem, Takao Inoue, Steven Kuntz, Ted Ririe, Erich Schwarz, Adeline Seah, and Weiwei Zhong for comments on the manuscript. Author contributions. JSF and PWS conceived and designed the experiments, analyzed the data, and wrote the paper. JSF performed the experiments. Funding. The authors were supported by the Howard Hughes Medical Institute of which PWS is an investigator. Competing interests. The authors have declared that no competing interests exist. The WormBase Gene IDs (www.wormbase.org) as well as the Refseq accession numbers (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide) for the genes described in this study are ajm-1:WBGene00000100 (NM_077135; NM_077137; NM_077136; NM_171966); cdh-3:WBGene00000395 (NM_066286); ceh-2:WBGene00000429 (NM_059345); cog-1:WBGene00000584 (NM_182115); eff-1:WBGene00001159 (NM_001026819); egl-17:WBGene00001185( NM_075706); egl-26:WBGene00001193 (NM_061251); egl-38:WBGene00001204 (NM_069435); lin-3:WBGene00002992 (NM_171418;NM_171919;NM_171918); lin-11:WBGene00003000 (NM_060295); nhr-67: WBGene00003657 (NM_069693); pax-2:WBGene00003938 (NM_068112); unc-53: WBGene00006788 (NM_001027000;NM_001026999); and zmp-1:WBGene00006987 (NM_171138).|
|Official Citation:||Fernandes JS, Sternberg PW (2007) The tailless Ortholog nhr-67 Regulates Patterning of Gene Expression and Morphogenesis in the C. elegans Vulva. PLoS Genet 3(4): e69 doi:10.1371/journal.pgen.0030069|
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|Deposited On:||17 Jul 2007|
|Last Modified:||26 Dec 2012 09:36|
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