title: Identification of Wnt Pathway Target Genes Regulating the Division and Differentiation of Larval Seam Cells and Vulval Precursor Cells in Caenorhabditis elegans.
abstract: The evolutionarily conserved Wnt/β-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 β-catenin and upregulation of target gene expression to mediate a cellular response. During larval development of the nematode Caenorhabditis elegans, Wnt/β-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.
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland 21250.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Gorrepati
authors.affiliation: Intramural Research Program, NIDDK, Bethesda, Maryland 20814.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Krause
authors.affiliation: Intramural Research Program, NIDDK, Bethesda, Maryland 20814.
authors.forename: Weiping
authors.initials: W
authors.lastname: Chen
authors.affiliation: Intramural Research Program, NIDDK, Bethesda, Maryland 20814.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Brodigan
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland 21250.
authors.forename: Margarita
authors.initials: M
authors.lastname: Correa-Mendez
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland 21250 eisenman@umbc.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Eisenmann
mesh_terms: D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D017930:Genes, Reporter; D007814:Larva / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013696:Temperature; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014844:Vulva / Q000254:growth & development / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; C097533:Lin-1 protein, C elegans; D012333:RNA, Messenger; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C115024:cki-1 protein, C elegans; C101878:pak-1 protein, C elegans; D047390:Casein Kinase II; C000590648:Kin-10 protein, C elegans; D054462:p21-Activated Kinases
keywords: C. elegans; Wnt signaling; differentiation; mRNA tagging; seam cells; vulval precursor cells