title: MEX-3 interacting proteins link cell polarity to asymmetric gene expression in Caenorhabditis elegans.
abstract: The KH domain protein MEX-3 is central to the temporal and spatial control of PAL-1 expression in the C. elegans early embryo. PAL-1 is a Caudal-like homeodomain protein that is required to specify the fate of posterior blastomeres. While pal-1 mRNA is present throughout the oocyte and early embryo, PAL-1 protein is expressed only in posterior blastomeres, starting at the four-cell stage. To better understand how PAL-1 expression is regulated temporally and spatially, we have identified MEX-3 interacting proteins (MIPs) and characterized in detail two that are required for the patterning of PAL-1 expression. RNA interference of MEX-6, a CCCH zinc-finger protein, or SPN-4, an RNA recognition motif protein, causes PAL-1 to be expressed in all four blastomeres starting at the four-cell stage. Genetic analysis of the interactions between these mip genes and the par genes, which provide polarity information in the early embryo, defines convergent genetic pathways that regulate MEX-3 stability and activity to control the spatial pattern of PAL-1 expression. These experiments suggest that par-1 and par-4 affect distinct processes. par-1 is required for many aspects of embryonic polarity, including the restriction of MEX-3 and MEX-6 activity to the anterior blastomeres. We find that PAL-1 is not expressed in par-1 mutants, because MEX-3 and MEX-6 remain active in the posterior blastomeres. The role of par-4 is less well understood. Our analysis suggests that par-4 is required to inactivate MEX-3 at the four-cell stage. Thus, PAL-1 is not expressed in par-4 mutants because MEX-3 remains active in all blastomeres. We propose that MEX-6 and SPN-4 act with MEX-3 to translate the temporal and spatial information provided by the early acting par genes into the asymmetric expression of the cell fate determinant PAL-1.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Nancy N
authors.initials: NN
authors.lastname: Huang
authors.forename: Darcy E
authors.initials: DE
authors.lastname: Mootz
authors.forename: Albertha J M
authors.initials: AJ
authors.lastname: Walhout
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hunter
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D016764:Cell Polarity; D004338:Drug Combinations; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins; D009821:Oils; D010636:Phenols; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015534:Trans-Activators
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D004338:Drug Combinations; D015801:Helminth Proteins; D018398:Homeodomain Proteins; C102175:MEX-3 protein, C elegans; C410587:MEX-5 protein, C elegans; C410589:MEX-6 protein, C elegans; D009821:Oils; C027222:P & S Liquid; D010636:Phenols; D016601:RNA-Binding Proteins; C442231:SPN-4 protein, C elegans; D015534:Trans-Activators; C068665:pal-1 protein, C elegans; C409406:PAR-1 protein, C elegans; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases