The Gram-negative soil bacterium Myxococcus xanthus has a complex life cycle that includes vegetative growth and development (FIG. 1). During its life cycle, a myxo- bacterium exhibits social interactions of the type that are usually associated with more complex eukaryotic cells 1 , which has led to the use of M. xanthus as a model system for the study of social interactions and their regu- lation. M. xanthus grow by scavenging nutrients from decomposing soil and detritus, or by predation of other microorganisms 2–5 . M. xanthus cells lack flagella and are non-motile in liquid growth media, but can move on solid growth substrates at speeds of 2–4 µm per minute. This is extremely slow compared with other species such as Escherichia coli, which swims at a rate of ~50 µm per second 6 , and Flavobacterium johnsoniae, which glides at 5–10 µm per second 7 . M. xanthus cells are usually present in biofilms that consist of cells that are organized into a series of layers. The clustering of cells into organized groups known as swarms (FIG. 2a) facilitates predation and food gathering, because numerous bacteria cooperate to produce antibi- otics and digestive enzymes 8 . These antibiotics and lytic enzymes kill and digest prokaryotic and eukaryotic micro- organisms. Indeed, an estimated 8% of the M. xanthus genome is dedicated to the production of secondary metabolites, and at least 18 gene clusters specify the pro- duction of polyketide antibiotics — almost twice as many as the number of genes that specify antibiotic production in Streptomyces coelicolor 9 , which is a model for antibi- otic production. Furthermore, the M. xanthus genome encodes numerous proteases, nucleases and lipases that function in the digestion of macromolecules. Predation usually requires direct contact with the prey cells 10 , and this contact triggers the myxobacterial rippling response 5,11 (FIG. 2b). Rippling is the coordinated rhythmic movement of cells that is observed when myxobacteria feed on macromolecules or during the autolysis of cells that is associated with starvation and development 11–13 . Rippling creates ‘accordion waves’ (REF. 14) (FIG. 2c) in which cells seem to form a travelling wave. However, when the cells of two waves contact each other, cell reversals are induced that result in the two waves reflecting off each other. Berleman et al. 11 proposed that the function of travelling waves is to move cells back and forth, which might provide an efficient mechanism to ‘mop-up’ macromolecules from the surface and ensure efficient usage of growth substrates. Cells do not ripple when grown on rich media that lack macromolecules or lysed cells 11 . When M. xanthus swarms cannot find sufficient nutrients or prey, they enter a developmental pathway that results in the formation of multicellular mounds, which develop into fruiting bodies (FIG. 1,2d). During this process, gene expression and the pattern of cell move- ments are highly regulated. Cells aggregate into streams that merge to form fruiting bodies that are 0.1–0.2 mm in height, and each contain 10 5 –10 6 cells. In the fruit- ing bodies, most of the cells differentiate into spores, although some cells (about 10%), named peripheral rods, remain undifferentiated and are present as a monolayer of rod-shaped cells around and between fruiting bodies (FIG. 2e). Unfortunately, nothing is known about the ‘sig- nals’ that maintain this subpopulation of undifferenti- ated cells. Peripheral cells most likely function as ‘scout cells’ that identify new food sources, because they move about between fruiting bodies and maintain their veg- etative behaviour under starvation conditions 14,15 . The soluble nutrients that are released through digestion of food or prey by the peripheral rods might trigger spore germination in the fruiting body. *Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3204, USA. ‡ Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA. § Department of Microbiology, University of Iowa, Iowa City, Iowa 52242, USA. Correspondence to D.R.Z. and J.R.K. e-mails: zusman@berkeley. edu; john-kirby@uiowa.edu doi:10.1038/nrmicro1770 Published online 8 October 2007 Development A programmed change in gene expression and morphology. In Myxococcus xanthus, this process is triggered by starvation and results in cellular aggregation, fruiting-body formation and sporulation. Rippling Coordinated rhythmic movement of cells. Cell reversal When a cell changes its direction along its long axis so that the leading cell pole becomes the lagging cell pole. Mound An early stage of development during which cells aggregate before sporulation. Chemosensory pathways, motility and development in Myxococcus xanthus David R. Zusman*, Ansley E. Scott*, Zhaomin Yang ‡ & John R. Kirby § Abstract | The complex life cycle of Myxococcus xanthus includes predation, swarming, fruiting-body formation and sporulation. The genome of M. xanthus is large and comprises an estimated 7,400 open reading frames, of which approximately 605 code for regulatory genes. These include eight clusters of chemotaxis-like genes that define eight chemosensory pathways, most of which have dedicated functions. Although many of these chemosensory pathways have a role in controlling motility, at least two of these pathways control gene expression during development. REVIEWS 862 | NOVEMBER 2007 | VOLUME 5 www.nature.com/reviews/micro © 2007 Nature Publishing Group