Transcriptional network underlying Caenorhabditis elegans vulval development

Abstract

The vulval development of Caenorhabditis elegans provides an opportunity to investigate genetic networks that control gene expression during organogenesis. During the fourth larval stage (L4), seven vulval cell types are produced, each of which executes a distinct gene expression program. We analyze how the expression of cell-type-specific genes is regulated. Ras and Wnt signaling pathways play major roles in generating the spatial pattern of cell types and regulate gene expression through a network of transcription factors. One transcription factor (lin-29) primarily controls the temporal expression pattern. Other transcription factors (lin-11, cog-1, and egl-38) act in combination to control cell-typespecific gene expression. The complexity of the network arises in part because of the dynamic nature of gene expression, in part because of the presence of seven cell types, and also because there are multiple regulatory paths for gene expression within each cell type.organogenesis ͉ signaling pathways ͉ transcription D evelopmental events are driven by spatially and temporally regulated gene expression. Understanding how complex patterns of expression are produced is therefore a critical part of deciphering mechanisms of development. In general, intercellular signaling mechanisms interact with a network of transcription factors to generate cell-type-specific patterns of gene expression. The late stage of Caenorhabditis elegans vulval development offers a useful model in which to study this process. During this period of vulval development, seven distinct cell types are produced that express unique combinations of genes. Over the last several years, a number of genes were discovered that are expressed in cell-type and stage-specific patterns in the vulva, and several transcription factors were found to regulate these genes. In this paper, we synthesize and extend our current knowledge of this genetic network.The C. elegans vulva connects the uterine lumen to the outside, allowing for passage of sperm and fertilized eggs (1). Vulval cells are generated postembryonically from precursor cells P3.p P4.p, P5.p, P6.p, P7.p, and P8.p [also called vulval precursor cells (VPC)]. During the mid-third larval (L3) stage, EGF and Notch signaling induces the middle three VPCs (P5.p, P6.p, and P7.p) to adopt vulval fates, whereas P3.p, P4.p, and P8.p fuse with the hypodermal syncytium, hyp7 (2-6).During the late-L3 to the early-L4 stage, P5.p, P6.p, and P7.p undergo two or three rounds of cell division to produce 22 nuclei (7) (Fig. 1A). These nuclei are in cells of seven types (vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF), as evidenced by subsequent morphogenetic movements and by the pattern of gene expression (8, 9) (Fig. 1B). The seven cell types that are present in the adult vulva represent specializations within the general epithelial cell class. These cells exhibit cell-type general features; for example, each expresses ajm-1, a component of the apical junction that connects neighboring cells in epithelial tissues (8)....

A novel candidate cis-regulatory motif pair in the promoters of germline and oogenesis genes in C. elegans

“…Among them are the promoters of terminal differentiation/selector genes of individual neurons (Hobert 2008), the transcriptional network underlying vulval development (Inoue et al 2005), and motifs in target genes of the TF PHA-4 that specifies pharyngeal identity (Gaudet and Mango 2002). In terms of length and distance from the TSS, the motifs we found resemble many known TFBS patterns in C. elegans and in other species.…”

Temporal ChIP-on-chip reveals Biniou as a universal regulator of the visceral muscle transcriptional network

“…7) that likely target different subsets of these CRMs. Such feed-forward regulation is a prevalent feature in many developmental networks (Davidson et al 2002;Schroeder et al 2004;Inoue et al 2005;Koide et al 2005;Sandmann et al 2007a).…”

Computational and Systems Biology

“…In C. elegans, direct transcription factor regulatory interaction networks have been identified through chromatin immunoprecipitation, 13,14 and yeast one-hybrid experiments, [15][16][17] while indirect regulatory interaction networks have mainly been identified through combinations of gene knockout or knockdown and gene reporter, RT-PCR or microarray experiments. [18][19][20][21] In the latter case, cis-regulatory motif finding algorithms have been applied in order to pinpoint the transcription factors directly responsible for the change in gene expression. 22 Reverse-engineering could significantly increase the knowledge on transcription regulatory networks in C. elegans and put forward a set of interactions worth the experimental time, cost and effort to validate them in vivo.…”