During the early stages of embryogenesis, cell polarity is established, which results in asymmetric gene expression that ultimately contributes to pattern formation and differentiation. Huang et al. used genetic manipulation of Caenorhabditis elegans to study mechanisms underlying the asymmetric expression of the PAL-1 gene in early embryos (2-cell to 22-cell stage). The PAL-1 transcript is ubiquitously distributed in the embryo, but the protein is restricted to the posterior cells. MEX-3 is an RNA binding protein that represses PAL-1 translation. Using a yeast two-hybrid screen, Huang et al. identified MEX-3 interacting proteins, which, when analyzed by genetic methods, were involved in the spatial regulation of PAL-1 expression. Additionally, genetic interactions were observed among the Mex-interacting proteins (MEX-6 and SPN-4), MEX-3, and the polarizing par genes, PAR-1, PAR-3, and PAR-4. RNA interference designed to inhibit MEX-6 appeared to inhibit both MEX-6 and a closely related gene MEX-5; thus, all interpretations assume inhibition of both of these genes. Based on the phenotypic analysis, analysis of PAL-1 distribution, and semiquantitative analysis of MEX-3 protein abundance, the authors propose a pathway for regulating the spatial and temporal expression of PAL-1. Anterior localization of PAR-3 restricts PAR-1 to the posterior cells, which restricts MEX-5 and MEX-6 the anterior cells. MEX-5 and MEX-6 stabilize MEX-3, which inhibits the translation of PAL-1. Thus, PAL-1 is limited to posterior cells. In the absence of MEX-5 and MEX-6, PAR-4 and SPN-4 appear to promote the degradation of MEX-3.
N. N. Huang, D. E. Mootz, A. J. M. Walhout, M. Vidal, C. P. Hunter, MEX-3 interacting proteins link cell polarity to asymmetric gene expression in Caenorhabditis elegans. Development 129, 747-759 (2002). [Online Journal]