Integrating transcriptional and signalling networks during muscle development Eileen E Furlong A fundamental aspect of developmental decisions is the ability of groups of cells to obtain the competence to respond to different signalling inputs. This information is often integrated with intrinsic transcriptional networks to produce diverse developmental outcomes. Studies in Drosophila are starting to reveal a detailed picture of the regulatory circuits controlling the subdivision of the dorsal mesoderm, which gives rise to diverse muscle types including cardioblasts, pericardial cells, body wall muscle and gut muscle. The combination of a common set of mesoderm autonomous transcription factors (e.g. Tinman and Twist) and spatially restricted inductive signals (e.g. Dpp and Wg) subdivide the dorsal mesoderm into different competence domains. The integration of additional signalling inputs with localised repression within these competence domains results in diverse transcriptional responses within neighbouring cells, which in turn generates muscle diversity. Addresses Developmental Biology and Gene Expression Programmes, EMBL, Heidelberg, Germany e-mail: furlong@embl.de Current Opinion in Genetics & Development 2004, 14:343–350 This review comes from a themed issue on Pattern formation and developmental mechanisms Edited by Derek Stemple and Jean-Paul Vincent Available online 20th June 2004 0959-437X/$ – see front matter ß 2004 Elsevier Ltd. All rights reserved. DOI 10.1016/j.gde.2004.06.011 Abbreviations ChIP chromatin immunoprecipitation DER epidermal growth factor receptor DMef2 Drosophila Myocyte enhancing factor 2 Dpp Decapentaplegic EGF epidermal growth factor Eve Evenskipped FGF fibroblast growth factor Htl Heartless HMG-D high-mobility-group protein-D L’sc Lethal of scute Mad Mothers against dpp MAPK mitogen-activated protein kinase RTK receptor tyrosine kinase Ush U-shaped slp sloppy paired Wg Wingless Introduction The precise mechanism of how diverse cell fates are specified from the same group of precursors is a long- standing question in developmental biology. Genetic studies have shown that a substantial amount of regula- tion of cell-fate specification occurs at the level of tran- scriptional control. This is especially true in the case of muscle development, where a large number of transcrip- tion factors have been identified that regulate the pro- gressive subdivision of the mesoderm and the subsequent specification of different muscle types. The Drosophila dorsal mesoderm has become a good model system to study how diverse muscle types are derived from a common pool of dorsal myoblasts, within the developing embryo. The combined activities of signalling pathways (Dpp and Wg) with tissue specific transcription factors (Twist and Tinman) subdivide the dorsal mesoderm into different competence domains, which result in different equivalence groups of cells. Single progenitor cells are then selected within these equivalence groups by Notch- mediated lateral inhibition and Ras signalling. These later aspects of myoblast specification are not discusssed in this review, which focusses instead on the transcrip- tional regulatory code that is used to generate different equivalent groups, or muscle primordia, within the same population of precursor cells. Substantial progress has been made in the identification of progenitor cells for different dorsal muscle types. Each progenitor expresses a specific transcription factor or combination of transcription factors, referred to as iden- tity genes, that are essential for that muscle cell’s spe- cification (reviewed in [1–3]). Although the regulation of expression for only a small number of these identity genes has been studied in detail, we can use this infor- mation to begin to decipher the complex regulatory code leading to dorsal muscle diversity. Even for the expres- sion of a single progenitor-identity transcription factor, the combinatorial action of multiple transcription factors as well as the integration of converging signalling net- works are required. The specification of two muscle cell types from the dorsal mesoderm; the tinman-expressing cardioblast and the eve-expressing pericardial cell, are discussed in detail with the aim of understanding the nature of the transcriptional circuitry used to produce different developmental outputs using the same tran- scriptional inputs. The dorsal mesoderm gives rise to diverse muscle cell types The Drosophila heart or dorsal vessel is a relatively simple linear tube, comprising two main cell types: cardioblasts and pericardial cells, both of which have further divers- ity based on expression of specific progenitor-identity www.sciencedirect.com Current Opinion in Genetics & Development 2004, 14:343–350