MEX-3 interacting proteins link cell polarity to asymmetric gene expression inCaenorhabditis elegans

• DOI: 10.1242/dev.129.3.747
• Publication Date: 2021-04-25T13:43:27Z
• Authors: Nancy N. Huang; Darcy E. Mootz; Albertha J. M. Wa...; Marc Vidal; Craig P. Hunter
• Keywords: 571; Cell Cycle Proteins; Protein Serine-Threonine Kinases; 03 medical and health sciences; Phenols; Helminth; Animals; Developmental; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Genes, Helminth; Homeodomain Proteins; 0303 health sciences; Cell Polarity; Gene Expression Regulation, Developmental; RNA-Binding Proteins; *Cell Polarity; Genetics and Genomics; Helminth Proteins; Protein-Serine-Threonine Kinases; Drug Combinations; Gene Expression Regulation; Genes; *Trans-Activators; Trans-Activators; *Homeodomain Proteins; Oils

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.