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Cited by 20Developmental Biology and Gene RegulationNeurobiology and Insect Physiology ResearchGenomics and Chromatin Dynamics

E93 controls adult differentiation by repressing broad in Drosophila

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Cruz, Josefa, Ureña, Enric, Iñiguez, Luis P., Irimia, Manuel, Franch-Marro, Xavier, Martín, David·2024·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2403162121PMC PMC11665871
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Abstract

In Drosophila melanogaster , successful development relies on the precise coordination of both spatial and temporal regulatory axes. The temporal axis governs stage-specific identity and developmental transitions through a number of genes, collectively forming the Metamorphic Gene Network . Among these, Ecdysone inducible protein 93F (E93) serves as the critical determinant for adult specification, but its mechanism of action remains unclear. Here, we found that, rather than acting mainly as an instructive signal, E93 promotes adult differentiation through the repression of the pupal specifier broad ( br ). In the absence of E93, sustained high levels of Br during the pupal stage strongly represses pupal-specific enhancers that are essential for the terminal differentiation of the wing. Notably, RNA-seq analysis confirmed that the majority of E93-dependent transcriptomic changes in pupal wings are primarily driven by br repression. In addition, we also show that Br represses the pupal-enhancers during the larval and prepupal stages preventing the premature implementation of the adult genetic program, and that it also dampens the activity of larval enhancers during the latter stages of larval development. This mechanism of action seems to be a derived feature acquired in Diptera, as in the coleopteran Tribolium castaneum , repression of br by E93 is not sufficient to allow adult differentiation. In summary, our study elucidates the crucial role of the intricate interplay between E93 and Br as the governing mechanism in the process of terminal differentiation in Drosophila . This finding holds significant implications for advancing our understanding of the evolution of insect metamorphosis.

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  • When E93 was selectively knocked down in the pupal wing, the mutant region arrested development but also showed elevated and sustained expression of Broad.

    “When E93 was selectively knocked down in the pupal wing, the mutant region arrested development but also showed elevated and sustained expression of Broad.”

    From Regulation of metamorphosis in holometabolous insects (2026) · cites this paper as [11]

    The Results section reports that selective E93 depletion in the wing caused significant impairment of terminal adult differentiation and persistently elevated Br during the pupal period. It also reports sustained high Br in specifically depleted wing compartments. It does not describe the mutant region as having arrested development; the depleted wings still developed, although with defects. (LLM, conf=0.83)

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  • Knockdown of E93 allows persistence of Broad, thereby maintaining suppression of these genes.

    “The knockdown of E93 allows the persistence of Broad, thereby maintaining suppression of these genes.”

    From Regulation of metamorphosis in holometabolous insects (2026) · cites this paper as [11]

  • A major way that E93 evokes adult development in Drosophila is through the removal of Broad suppression.

    “These findings suggest that a major way that E93 evokes adult development in Drosophila is through the removal of Broad suppression.”

    From Regulation of metamorphosis in holometabolous insects (2026) · cites this paper as [11]

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Authors
Cruz, J., Ureña, E., Iñiguez, L. P., Irimia, M., Franch-Marro, X., & Martín, D.
Affiliations
  • Consejo Superior de Investigaciones Científicas (ES)
  • Universitat Pompeu Fabra (ES)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
  • Institute of Evolutionary Biology, Spanish National Research Council (CSIC)-Universitat Pompeu Fabra
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2024-12-13
Volume
121
Issue
51
Pages
e2403162121-e2403162121
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2403162121
PMC
PMC11665871
OpenAlex
W4405366096
Cited by
20
References
3
Citations by year
2026: 12 · 2025: 7 · 2024: 1
FWCI
2.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (publishedVersion, cc-by-nc-nd)
Funders
  • Ministerio de Ciencia, Innovación y Universidades (PGC2018-098427-B-I00, PID2021-125661NB-100, PGC2020:PID2020-115040 GB-I00, IJC2020-044783-I)
  • Government of Catalonia | Agència de Gestió d'Ajuts Universitaris i de Recerca (2017-SGR 1030, 2021-SGR 0417)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
E93, Broads, pupal wings, developmental timing, enhancer repression, terminal differentiation, insect metamorphosis, Diptera, Tribolium castaneum, Drosophila melanogaster
MeSH terms
Animals, Cell Differentiation, Drosophila melanogaster, Larva, Metamorphosis, Biological, Pupa, Transcription Factors, Wings, Animal, Gene Expression Regulation, Developmental, Drosophila Proteins

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