Asymmetric cell division entails the unequal separation of components between daughter cells. When this includes factors that regulate gene expression, the two daughter cells can run different genetic programs. Cellular asymmetry underlies basic developmental mechanisms such as tissue differentiation and stem cell maintenance, and is therefore critical for multicellular life. Interestingly, many bacteria are also capable of asymmetric cell division, and just as in animal cells, cell division produces two morphologically and transcriptionally distinct cell types - a basic form of multicellularity.

In Caulobacter crescentus, asymmetry is created by the establishment of two distinct multiprotein complexes at opposite cell poles. The localized proteins include at least seven histidine kinases and response regulators, a protease complex, and a host of other factors, and all of these work together to establish a robust pattern of asymmetric gene expression in the daughter cells. Such a sophisticated mechanism must have originated from a simpler form, but its complexity makes it difficult to deduce the basic framework. What are the minimal components needed to establish cellular asymmetry and generate differential gene expression, and how could such a mechanism have evolved?

An attractive starting point for addressing these questions is the polar organizing protein PopZ. PopZ is an essential component of the polar multiprotein complexes in Caulobacter crescentus. The gene is conserved through alpha-proteobacteria, indicating inheritance from an early stage of prokaryotic evolution.

Interestingly, PopZ shows a strong tendency to accumulate at a single pole when expressed heterologously in E. coli, an unrelated species without robust asymmetry or cell polarity. We are testing the hypothesis that PopZ was an early player in the evolution of cellular asymmetry in the alpha-proteobacterial lineage, and that it is part of a core polarity mechanism from which more elaborate systems have evolved. Can PopZ be used to build simple polarized signaling complexes in E. coli and can they be used to drive asymmetric gene expression in this system?

Luis Comolli, LBNL