A juvenile hormone agonist reveals distinct developmental pathways mediated by ecdysone-inducible Broad Complex transcription factors

Linda L Restifo, Thomas G. Wilson

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Juvenile hormone (JH) is an important regulator of insect development that, by unknown mechanisms, modifies molecular, cellular, and organismal responses to the molting hormone, 20-hydroxyecdysone (20E). In dipteran insects such as Drosophila, JH or JH agonists, administered at times near the onset of metamorphosis, cause lethality. We tested the hypothesis that the JH agonist methoprene acts by interfering with function of the Broad Complex (BRC), a 20E-regulated locus encoding BTB/POZ-zinc finger transcription factors essential for metamorphosis of many tissues. We found that methoprene, administered by feeding or by topical application, disrupts the metamorphic reorganization of the central nervous system, salivary glands, and musculature in a dose-dependent manner. As we predicted, methoprene phenocopies a subset of previously described BRC defects; it also phenocopies Deformed and produces abnormalities not associated with known mutations. Interestingly, methoprene specifically disrupts those metamorphic events dependent on the combined action of all BRC isoforms, while sparing those that require specific isoform subsets. Thus, our data provide independent pharmacological evidence for the model, originally based on genetic studies, that BRC proteins function in two developmental pathways. Mutations of Methoprene-tolerant (Met), a gene involved in the action of JH, protect against all features of the 'methoprene syndrome.' These findings have allowed us to propose novel alternative models linking BRC, juvenile hormone, and MET.

Original languageEnglish (US)
Pages (from-to)141-159
Number of pages19
JournalDevelopmental Genetics
Volume22
Issue number2
DOIs
StatePublished - 1998

Fingerprint

Methoprene
Ecdysone
Juvenile Hormones
Transcription Factors
Insects
Protein Isoforms
Ecdysterone
Mutation
Zinc Fingers
Salivary Glands
Drosophila
Central Nervous System
Pharmacology

Keywords

  • Broad Complex
  • Central nervous system
  • Deformed
  • Drosophila
  • Ecdysone
  • Juvenile hormone
  • Met
  • Metamorphosis
  • Methoprene

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Genetics

Cite this

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abstract = "Juvenile hormone (JH) is an important regulator of insect development that, by unknown mechanisms, modifies molecular, cellular, and organismal responses to the molting hormone, 20-hydroxyecdysone (20E). In dipteran insects such as Drosophila, JH or JH agonists, administered at times near the onset of metamorphosis, cause lethality. We tested the hypothesis that the JH agonist methoprene acts by interfering with function of the Broad Complex (BRC), a 20E-regulated locus encoding BTB/POZ-zinc finger transcription factors essential for metamorphosis of many tissues. We found that methoprene, administered by feeding or by topical application, disrupts the metamorphic reorganization of the central nervous system, salivary glands, and musculature in a dose-dependent manner. As we predicted, methoprene phenocopies a subset of previously described BRC defects; it also phenocopies Deformed and produces abnormalities not associated with known mutations. Interestingly, methoprene specifically disrupts those metamorphic events dependent on the combined action of all BRC isoforms, while sparing those that require specific isoform subsets. Thus, our data provide independent pharmacological evidence for the model, originally based on genetic studies, that BRC proteins function in two developmental pathways. Mutations of Methoprene-tolerant (Met), a gene involved in the action of JH, protect against all features of the 'methoprene syndrome.' These findings have allowed us to propose novel alternative models linking BRC, juvenile hormone, and MET.",
keywords = "Broad Complex, Central nervous system, Deformed, Drosophila, Ecdysone, Juvenile hormone, Met, Metamorphosis, Methoprene",
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AU - Wilson, Thomas G.

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N2 - Juvenile hormone (JH) is an important regulator of insect development that, by unknown mechanisms, modifies molecular, cellular, and organismal responses to the molting hormone, 20-hydroxyecdysone (20E). In dipteran insects such as Drosophila, JH or JH agonists, administered at times near the onset of metamorphosis, cause lethality. We tested the hypothesis that the JH agonist methoprene acts by interfering with function of the Broad Complex (BRC), a 20E-regulated locus encoding BTB/POZ-zinc finger transcription factors essential for metamorphosis of many tissues. We found that methoprene, administered by feeding or by topical application, disrupts the metamorphic reorganization of the central nervous system, salivary glands, and musculature in a dose-dependent manner. As we predicted, methoprene phenocopies a subset of previously described BRC defects; it also phenocopies Deformed and produces abnormalities not associated with known mutations. Interestingly, methoprene specifically disrupts those metamorphic events dependent on the combined action of all BRC isoforms, while sparing those that require specific isoform subsets. Thus, our data provide independent pharmacological evidence for the model, originally based on genetic studies, that BRC proteins function in two developmental pathways. Mutations of Methoprene-tolerant (Met), a gene involved in the action of JH, protect against all features of the 'methoprene syndrome.' These findings have allowed us to propose novel alternative models linking BRC, juvenile hormone, and MET.

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