The Drosophila nuclear receptors DHR3 and βFTZ-F1 control overlapping developmental responses in late embryos

Abstract

SUMMARYStudies of the onset of metamorphosis have identified an ecdysone-triggered transcriptional cascade that consists of the sequential expression of the transcription-factor-encoding genes DHR3, FTZ-F1, E74A and E75A. Although the regulatory interactions between these genes have been well characterized by genetic and molecular studies over the past 20 years, their developmental functions have remained more poorly understood. In addition, a transcriptional sequence similar to that observed in prepupae is repeated before each developmental transition in the life cycle, including mid-embryogenesis and the larval molts. Whether the regulatory interactions between DHR3, FTZ-F1, E74A and E75A at these earlier stages are similar to those defined at the onset of metamorphosis, however, is unknown. In this study, we turn to embryonic development to address these two issues. We show that mid-embryonic expression of DHR3 and FTZ-F1 is part of a 20-hydroxyecdysone (20E)-triggered transcriptional cascade similar to that seen in mid-prepupae, directing maximal expression of E74A and E75A during late embryogenesis. In addition, DHR3 and FTZ-F1 exert overlapping developmental functions at the end of embryogenesis. Both genes are required for tracheal air filling, whereas DHR3 is required for ventral nerve cord condensation and FTZ-F1 is required for proper maturation of the cuticular denticles. Rescue experiments support these observations, indicating that DHR3 has essential functions independent from those of FTZ-F1. DHR3 and FTZ-F1 also contribute to overlapping transcriptional responses during embryogenesis. Taken together, these studies define the lethal phenotypes of DHR3 and FTZ-F1 mutants, and provide evidence for functional bifurcation in the 20E-responsive transcriptional cascade.

Temporally tuned neuronal differentiation supports the functional remodeling of a neuronal network in Drosophila

“…Previous studies demonstrated that ftz-f1 dictates the temporal specificity of ecdysone signaling by integrating messages between numerous nuclear receptors (E75, DHR3, DHR4, and potentially also E78 and DHR39) (36,37). Despite its long-known expression in the nervous system, the only reported role for ftz-f1 in nervous system metamorphosis, to our knowledge, is in the remodeling of mushroom body neuron morphology (47)(48)(49)(50). Here, we describe a role for ftz-f1 in triggering timed neuronal differentiation.…”

Recent advances in understanding mechanisms of insect cuticle differentiation

“…Indeed, mutations in the genes coding for the enzymes that convert cholesterol into 20-hydroxyecdysone, the active form of ecdysone, cause developmental arrest at mid-embryogenesis and formation of a very reduced cuticle (Chavez et al, 2000;Ono et al, 2006;Petryk et al, 2003). The phenotypes of ecdysone-deficient embryos are strong compared to those resulting from defects in ecdysone transduction mediated for example by E75 or b-FtzF1 (Reinking et al, 2005;Ruaud et al, 2010) arguing that multiple transcription factors cooperate to transduce the ecdysone signal during cuticle differentiation. It will be a great and fruitful challenge to dissect these pathways downstream of ecdysone in the D. melanogaster embryo.…”

SAYP interacts with DHR3 nuclear receptor and participates in ecdysone-dependent transcription regulation

“…We have directly shown that DHR3, via the interaction with SAYP, drives the expression of several SAYP-dependent genes in cell culture. The above genes have not been recognized as components of the ecdysone cascade, 15 which is evidence that the effect of ecdysone stimulation may be much wider than expected previously. transcription before and after DHR3 induction with ecdysone (Fig.…”

“…DHR3 is essential in embryogenesis, during larval development and in the initiation of metamorphosis. [15][16][17] Although the biological function of DHR3 in Drosophila development has been well characterized, the molecular mechanism of its action has remained obscure.…”