**1.4 Linking the Ecdysone pulse to cell cycle**

In *Drosophila*, cell growth and cell cycle progression are regulated by a number of key genes, which have been shown to control the cell cycle in an analogous manner in all multicellular organisms. These include the *Drosophila* orthologue of the mammalian *c-myc* transcription factor and oncogene, dMyc, which drives growth and progression through G1 to S-phase (Johnston et al. 1999), the essential G1 to S-phase Cyclin complex, Cyclin E (CycE) and its Cyclin-dependent-kinase (Cdk) partner Cdk2, which triggers S-phase by promoting DNA replication (Knoblich et al. 1994; Neufeld et al. 1998; Richardson et al. 1995), and the *Drosophila* orthologue of the Cdc25 phosphatase, String (Stg), which is required for G2/M progression and promotes mitotic entry by activating the Cdk1/Cyclin B complex (Edgar and Datar 1996). CycE and Stg are the rate limiting factors for S-phase and mitosis, respectively, and both are activated by the *Drosophila* orthologue of human E2F1 protein, dE2F1 (Neufeld et al. 1998). dE2F1 responds to the relevant Cdk-Cyclin complex (CycE/Cdk2 for S-phase and CycB/Cdk1 for mitosis) to coordinate cell cycle progression from G1 to S-phase and G2 into mitosis (Reis and Edgar 2004).

During metamorphosis, following removal of the obsolete larval structures, proliferation of the remaining tissue occurs in an ecdysone-dependent manner to produce adult structures. For example, during pupal development the larval midgut is removed by apoptosis and is replaced through proliferation of the remaining tissue to form the adult midgut (Jiang, Baehrecke, and Thummel 1997). Microarray analysis has revealed that the ecdysone signal is associated with the activation of key cell cycle genes, including *Cyclin B, Cdc2* and *Cyclin D*, during the initiation of midgut metamorphosis (Li and White 2003). Analysis of *EcR* null mutants also revealed that EcR function was necessary for the cell cycle and growth genes to be activated in the larval midgut, suggesting that the ecdysone pathway is required for cell division control. The body of this chapter will discuss how the ecdysone pulse achieves changes to cell growth and cell cycle progression. First we will describe how ecdysone levels dictate body size cell extrinsically by controlling developmental timing. Then we will discuss how ecdysone works with its receptors, in a tissue autonomous manner to control transcription of cell cycle genes, which most likely occurs indirectly by modifying the activity of developmental signalling pathways.
