Ecdysone Receptor

K. S. Sowmiya Rani

Figure 18.21Regulation of insect metamorphosis. (A) Structures of juvenile hormone, ecdysone, and the active molting hormone 20-hydroxyecdysone. (B) General pathway of insect metamorphosis. Ecdysone and juvenile hormone together cause molts to keep the status quo and form another larval instar. When there is a lower concentration of juvenile hormone, the ecdysone-induced molt produces a pupa. When ecdysone acts in the absence of juvenile hormone, the imaginal discs differentiate, and the molt gives rise to the adult. (After Gilbert and Goodman 1981.)From: Metamorphosis: The Hormonal Reactivation of Development

Developmental Biology. 6th edition.Gilbert SF.Sunderland (MA): Sinauer Associates; 2000.

Ecdysone Ecdysone ReceptorReceptor

Non-covalent heterodimer of EcR protein and ultraspiracle protein (USP)- both represented by single genes.

Orthologs of the mammalian farnesoid X receptor (FXR) and retinoid X receptor (RXR) proteins, respectively

Term USP reserved for lepidopteran and dipteran insects RXR in other insects

They share the multi-domain architecture common to all nuclear hormone receptors

N-terminal transcriptional activation domain (A/B domain) DNA-binding domain (C domain, highly conserved between receptors) a linker region (D region) ligand-binding domain (E domain, moderately conserved) IN SOME CASES IN SOME CASES a distinct C-terminal extension (F-domain)

• 20-hydroxyecdysone cannot bind to DNA by itself

• Only one type of gene for USP/ EcR have been identified so far

Figure 18.22Formation of the ecdysone receptors. Alternative mRNA splicing of the ecdysone receptor (EcR) transcript creates three types of EcR mRNAs. These generate proteins having the same DNA-binding site (blue) and hydroxyecdysone-binding site (red), but with very ifferent amino termini. (After Talbot et al. 1993.)

From: Metamorphosis: The Hormonal Reactivation of Development

Developmental Biology. 6th edition.Gilbert SF.Sunderland (MA): Sinauer Associates; 2000.

• Early response genesE74E75Broad-complex

• Late response genesL63 - homology to CDK protein

family/ required for Drosophila development

L71 - set of antimicrobial peptides/ defense during metamorphosis

L82 - mutational studies/ developmental delay and eclosion lethal phenotypes

(a) Three pathways, including TGF-β signaling, the cohesin protein complex and the FTZ-F1 nuclear receptor, are essential for the upregulation of EcR-B1 before the pre-pupal ecdysone peak. (b) Binding of ecdysone to the EcR-B1/USP heterodimeric complex then triggers axon pruning, which involves microtubule disruption, axon degeneration and engulfment of fragmented axons by glia.

Figure 1: Schematic model of axon pruning during Drosophila metamorphosis.

neurons in the insect central nervous system release prothoracicotropic hormone (PTTH)

This neuropeptide signals the adjacent ring gland to secrete the steroid hormone ecdysone into the hemolymph of the circulatory system

Some peripheral tissues, most notably the larval fat body, modify ecdysone into its biologically active form, 20-hydroxyecdysone.

This hormone can then directly regulate gene expression through its interaction with the ecdysone receptor.

Figure 1. The ecdysteroid titer profile during Drosophila development. The composite ecdysteroid titer is depicted, in 20-hydroxyecdysone equivalents from whole-body homogenates (44). Each of the developmental stages of the Drosophila life cycle are also shown, below a time scale in days. Reprinted with permission from Thummel (45).

Ref: http://what-when-how.com/molecular-biology/ecdysone-molecular-biology/

Figure 2. Temporal patterns of ecdysone-regulated gene expression during the onset of metamorphosis. A schematic representation of the ecdysone pulses is shown at the top, with the magnitude of each pulse represented by the width of the stippled bar. Developmental time proceeds from left to right, with the major ecdysone-triggered transitions marked by dotted lines. The dotted line on the left represents the second-to-third instar larval molt, and the dotted line on the right represents head eversion and the prepupal-pupal transition. Dark grey bars show the timing and duration of primary-response regulatory gene transcription, the light grey bar represents bFTZ-F1 transcription, and the black bars represent secondary-response gene transcription.

http://what-when-how.com/molecular-biology/ecdysone-molecular-biology/

Figure 3. Multiple ecdysone-triggered regulatory hierarchies direct the onset of Drosophila metamorphosis. This figure summarizes regulatory interactions discussed in the text. Bars represent repressive effects, and arrows represent inductive effects.

http://what-when-how.com/molecular-biology/ecdysone-molecular-biology/

OrthologsOrthologs• Homologous sequences are orthologous if they were separated by

a speciation event: when a species diverges into two separate species, the divergent copies of a single gene in the resulting species are said to be orthologous. Orthologs, or orthologous genes, are genes in different species that are similar to each other because they originated by vertical descent from a single gene of the last common ancestor.

• The strongest evidence that two similar genes are orthologous is the result of a phylogenetic analysis of the gene lineage

• Genes that are found within one clade are orthologs, and comprise an orthologous group of genes descended from a common ancestor.

• Orthologs often, but not always, have the same function

Figure 18.11Modes of insect development. Molts are represented as arrows. (A) Ametabolous (direct) development in a silverfish. After a brief pronymph stage, the insect looks like a small adult. (B) Hemimetabolous (gradual) metamorphosis in a cockroach. After a very brief pronymph phase, the insect becomes a nymph. After each molt, the next nymphal instar looks more like an adult, gradually growing wings and genital organs. (C) Holometabolous (complete) metamorphosis in a moth. After hatching as a larva, the insect undergoes successive larval molts until a metamorphic molt causes it to enter the pupal stage. Then an imaginal molt turns it into an adult.From: Metamorphosis: The Hormonal Reactivation of Development

Developmental Biology. 6th edition.Gilbert SF.Sunderland (MA): Sinauer Associates; 2000.