The Wnt signaling pathway plays a fundamental role during the development of metazoans, where it functions in the regulation of diverse processes including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin dependent or canonical Wnt signaling pathway upregulates expression of Wnt target genes to mediate an appropriate cellular response. In the nematode C. elegans, a Wnt signaling pathway similar to the canonical pathway regulates several processes during larval development, however few target genes of this pathway have been identified. To address this deficit, we conditionally activated Wnt signaling in living animals during a defined stage of larval life by expressing a dominant, activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared to control animals. In this way we identified 166 differentially expressed genes, of which 104 were upregulated. A subset of the upregulated genes were validated by qPCR and showed altered expression in Wnt pathway mutants with decreased or increased Wnt signaling; we consider these genes to be candidate Wnt pathway targets in the C. elegans hermaphrodite larva. Amongst these was a group of 6 genes, including the cuticular collagen genes, bli-1 col-38, col-49 and col-71, that show a peak of expression in the mid L4 stage during normal development. The L4 expression of these genes suggests they may be expressed for use in the adult cuticle, and consistent with this, reduction of function for several of the genes leads to phenotypes suggestive of defects in cuticle function or integrity. Therefore this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.
Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.
No sample metadata fields
View SamplesThe evolutionarily conserved Wnt/?-catenin signaling pathway plays a fundamental role during metazoan development, regulating numerous processes including cell fate specification, cell migration, and stem cell renewal. Wnt ligand binding leads to stabilization of the transcriptional effector ?-catenin and upregulation of target gene expression to mediate a cellular response. During larval development of the nematode Caenorhabditis elegans, Wnt/?-catenin pathways act in fate specification of two hypodermal cell types, the ventral vulval precursor cells (VPCs) and the lateral seam cells. Because little is known about targets of the Wnt signaling pathways acting during larval VPC and seam cell differentiation, we sought to identify genes regulated by Wnt signaling in these two hypodermal cell types. We conditionally activated Wnt signaling in larval animals and performed cell type?specific "mRNA tagging" to enrich for VPC and seam cell?specific mRNAs, and then used microarray analysis to examine gene expression compared to control animals. Two hundred thirty-nine genes activated in response to Wnt signaling were identified, and we characterized 50 genes further. The majority of these genes are expressed in seam and/or vulval lineages during normal development, and reduction of function for nine genes caused defects in the proper division, fate specification, fate execution, or differentiation of seam cells and vulval cells. Therefore, the combination of these techniques was successful at identifying potential cell type?specific Wnt pathway target genes from a small number of cells and at increasing our knowledge of the specification and behavior of these C. elegans larval hypodermal cells.
Identification of Wnt Pathway Target Genes Regulating the Division and Differentiation of Larval Seam Cells and Vulval Precursor Cells in Caenorhabditis elegans.
Specimen part
View SamplesThe present study reveals LMYC and MXD1 as novel regulators of a transcriptional program that is modulated during the maturation of Batf3-dependent dendritic cells (also known as type I classical dendritic cells or cDC1s).
The MYCL and MXD1 transcription factors regulate the fitness of murine dendritic cells.
Specimen part
View SamplesThis study set out to identify MLX transcriptional targets in muscle cells. C2C12 Myoblasts were virally transduced to increase MLX activity, by overexpression of the wild-type protein; and to decrease MLX activity by overexpression of a dominant negative MLX protein and by shRNA induced knockdown of MLX. Transcripts that were significantly and consistently regulated by the different modes of MLX modulation were identified. The largest proportion of these were genes encoding secreted proteins including growth factors, cytokines and extracellular proteins. We therefore conclude that MLX can regulate myokine transcripts. Overall design: mRNA profiles from C2C12 muscle cells with increased and decreased MLX activity were examined.
The glucose-sensing transcription factor MLX promotes myogenesis via myokine signaling.
No sample metadata fields
View SamplesThe goal of this study was to compare expression profiles of B cells in the presence and absence of transcription factor MAX under normal and premalignant settings Overall design: Each genotype is represented in triplicate (cells isolated from 3 individual mice for each)
<i>Max</i> deletion destabilizes MYC protein and abrogates Eµ-<i>Myc</i> lymphomagenesis.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
Age, Specimen part
View SamplesAnalysis of HSCs from control and c-myc N-myc deficient long-term hematopoietic stem cells. HSCs lacking both c-myc and N-myc display increased apoptosis rates. Data provide insight into the molecular changes occuring upon complete loss of Myc activity, clarifying the resulting apoptotic mechanism and the role of Myc family proteins in HSCs.
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
Age, Specimen part
View SamplesAnalysis of HSCs from control and c-myc N-myc deficient long-term hematopoietic stem cells. HSCs lacking both c-myc and N-myc display increased apoptosis rates. Data provide insight into the molecular changes occuring upon complete loss of Myc activity, clarifying the resulting apoptotic mechanism and the role of Myc family proteins in HSCs and commited progenitors.
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
Age, Specimen part
View SamplesTo identify the global gene expression changes driven by L-Myc during SCLC development, mRNA expression profiles were compared using total RNAs from preneoplastic precursors of SCLC and the cells transformed by overexpression of L-Myc.
Genetic requirement for Mycl and efficacy of RNA Pol I inhibition in mouse models of small cell lung cancer.
Specimen part
View SamplesWe sequenced mRNA from transverse slices of embryos from a variety of D. melanogaster mutants (bicoid over-expression, bicoid knockdown, hunchback knocdown, and zelda mutant) at the blastoderm stage to determine genome-wide patterns of gene expression. Overall design: mRNA from transverse sections of single D. melanogaster embryos mutant for patterning TFs was sequenced.
Genome-wide measurement of spatial expression in patterning mutants of <i>Drosophila melanogaster</i>.
Specimen part, Subject
View Samples