The KH domain protein MEX-3 is central to the temporal and spatial control of PAL-1 expression in the C. elegans

A central question in developmental biology is how cells first acquire polarity and then use that polarity to produce daughter cells with distinct patterns of gene expression. In C. elegans, the anteroposterior polarity of the zygote is determined by the position of the sperm pronucleus (Goldstein and Hird, 1996), which organizes a cortical and cytoplasmic rearrangement that leads to the asymmetric distribution of maternally supplied mRNAs and proteins before first cleavage (reviewed by Kemphues and Strome, 1997). Two broad classes of maternally expressed patterning genes have been identified in the C. elegans embryo: early acting polarity genes, which are required to establish or maintain embryonic polarity, and cell fate determinants, which act later to direct lineage-specific patterns of development (reviewed by Bowerman, 1998). Defects in polarity genes such as the par genes (partitioning defective) result in early and extensive polarity defects, including loss of asymmetry in cell size, cell cycle time, spindle orientation and distribution of cell fate determinants. Identified cell fate determinants include transcription factors and transmembrane receptors that are asymmetrically distributed among early blastomeres and are required to direct the differentiation of blastomere-specific cell lineages. While it is known that par gene activity is required to polarize the zygote and enable the proper segregation of cell fate determinants, the mechanisms of action are poorly understood. For example, PAR-1 and PAR-4 are cortically localized serine/threonine kinases; however, none of their phosphorylation targets is known (Guo and Kemphues, 1995; Watts et al., 2000). Similarly, par-3 and par-6 encode conserved PDZ domain proteins that apparently form a protein complex localized to the anterior cortex (Etemad-Moghadam et al., 1995; Hung and Kemphues, 1999; Joberty et al., 2000; Lin et al., 2000). However, the mechanism by which this PAR3/PAR-6 complex confers polarity information to downstream targets is largely unknown. We are interested in understanding how the PAR proteins direct the asymmetric distribution of maternally supplied cell fate determinants. Considering that maternal factors act to define asymmetries before zygotic transcription begins, the par-dependent distribution of maternal gene activities must be regulated by a variety of post-transcriptional mechanisms, including differential stability of RNA or protein, asymmetric RNA or 747 Development 129, 747-759 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV8907