Background Ecdysone triggers transcriptional changes via the ecdysone receptor (EcR) to

Background Ecdysone triggers transcriptional changes via the ecdysone receptor (EcR) to coordinate developmental programs of apoptosis, cell cycle and differentiation. and differentiation during margin wing development. involves proliferation, differentiation and death of larval tissues in order to form the adult fly. The major developmental hormone in larval wing imaginal disc has long served as an excellent system to elucidate connections between the activity of developmental signals and patterning of cell cycle gene expression, but potential mechanism(s) modulating these events via ecdysone/EcR remain a mystery. The wing disc is comprised of an epithelial sheet, which can be divided into distinct domains based on cell fate in the adult wing; the notum, hinge and pouch (Figure?1A). With the release of the ecdysone hormone at the end of the third instar, proliferation of the wing imaginal disc slows and differentiation of the adult sensory neurons begins along the presumptive wing margin [5,6]. Cell division is tightly coupled with differentiation in the cells comprising the wing margin, which undergo a cell cycle delay in order to pattern proneural gene expression in the clusters of sensory neuron precursor (SOP) cells required for differentiation and development of bristles [7,8]. However, a subset of margin cells must remain competent to re-enter the cycle as bristle precursors do not complete their final cell divisions until 24?hours After Puparium Formation (APF), by which time all epithelial cells of the wing have exited the cell cycle and most cells have arrested in G1 [5,6]. Thus for proper timing of wing margin development, cells spanning the dorsal-ventral (D/V) boundary must first undergo a coordinated cell cycle delay, but must also be competent to re-enter the cell cycle to complete bristle cell divisions during early pupal stages. Figure 1 Patterning cell cycle across the wing imaginal disc. (A) – Schematic of the 3rd instar wing disc. The red and blue region develops to form the notum and hinge while the purple region forms the wing blade. The green line marks the anterior-posterior (A/P) … Interactions between the Wingless (Wg) secreted morphogen and the Notch (N) receptor pathway have been implicated in this cell cycle patterning across the presumptive wing margin [9-12]. Although all cells at GR 38032F the D/V boundary are cell cycle delayed during the late third instar, patterning between the anterior and posterior compartments differs; posterior cells both within GR 38032F and immediately flanking the D/V boundary are delayed in G1, while the G1 band across the GR 38032F anterior of the boundary is flanked by G2 delayed cells (Figure?1B) [9-11,13,14]. During the transition from second to third instar, GR 38032F the D/V boundary is established through the activity of Notch signaling, via the Notch ligands Serrate and Delta, which lead to activation of expression [15-17]. Through an auto-inhibitory effect, Wg refines its own expression and also promotes expression of Delta and Serrate to create a positive-feedback loop that maintains Notch signaling and restricts Wg expression to the D/V boundary [18-20]. Wg signaling leads to the expression of proneural genes ((promoter lacks an required for G2-M progression. Ecdysone can SFRP2 also control animal growth rate via EcR-dependent expression of the growth and S-phase regulator dMyc in the fat body [27]. In this system, loss of EcR function in fat body results in elevated dMyc expression and increased growth, suggesting that EcR signaling normally represses dMyc. However, like the promoter, lacks an suggesting that the repression of dMyc is unlikely to occur via direct transcriptional regulation by EcR. Ecdysone pulses therefore control developmental timing and growth of a range of larval tissues [28-30], but how does ecdysone achieve these changes in cell growth and cell cycle progression? In particular, how does ecdysone connect with the major developmental signaling pathways that regulate cell cycle patterning in.