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Nat Rev Microbiol. 2015 Dec;13(12):749-60. doi: 10.1038/nrmicro3546. Epub 2015 Oct 26.

c-di-GMP signalling and the regulation of developmental transitions in streptomycetes.

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Department of Molecular Microbiology, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK.
Department of Microbiology, Institute for Biology, Humboldt University, 10115 Berlin, Germany.
Department of Biology, Lund University, Sölvegatan 35, 223 62 Lund, Sweden.


The complex life cycle of streptomycetes involves two distinct filamentous cell forms: the growing (or vegetative) hyphae and the reproductive (or aerial) hyphae, which differentiate into long chains of spores. Until recently, little was known about the signalling pathways that regulate the developmental transitions leading to sporulation. In this Review, we discuss important new insights into these pathways that have led to the emergence of a coherent regulatory network, focusing on the erection of aerial hyphae and the synchronous cell division event that produces dozens of unigenomic spores. In particular, we highlight the role of cyclic di-GMP (c-di-GMP) in controlling the initiation of development, and the role of the master regulator BldD in mediating c-di-GMP signalling.

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