Upregulation of E93 Gene Expression Acts as the Trigger for Metamorphosis Independently of the Threshold Size in the Beetle Tribolium castaneum
Open accessAbstract
Body size in holometabolous insects is determined by the size at which the juvenile larva undergoes metamorphosis to the pupal stage. To undergo larva-pupa transition, larva must reach a critical developmental checkpoint, the threshold size (TS); however, the molecular mechanisms through which the TS cues this transition remain to be fully characterized. Here, we use the flour beetle Tribolium castaneum to characterize the molecular mechanisms underlying entry into metamorphosis. We found that T. castaneum reaches a TS at the beginning of the last larval instar, which is associated with the downregulation of TcKr-h1 and the upregulation of TcE93 and TcBr-C. Unexpectedly, we found that while there is an association between TS and TcE93 upregulation, it is the latter that constitutes the molecular trigger for metamorphosis initiation. In light of our results, we evaluate the interactions that control the larva-pupa transition and suggest alternative models.
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Myoglianin and/or ecdysteroids cause broad expression.
“Myoglianin and/or ecdysteroids cause broad expression, and the decline in JH can stimulate E93.”
From Regulation of metamorphosis in holometabolous insects (2026) · cites this paper as [9]
The Introduction states that Broad complex is induced by ecdysone in the absence of juvenile hormone, supporting the ecdysteroid part of the claim with that qualification. Our copy does not identify myoglianin as a cause of Broad expression. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe JH decline evoked by crossing the threshold weight is sufficient to induce E93, but some other signal is needed for broad induction.
“Apparently, the JH decline evoked by crossing the threshold weight is sufficient to induce E93, but some other signal is needed for broad induction.”
From Regulation of metamorphosis in holometabolous insects (2026) · cites this paper as [9]
In “Size and Entry into Metamorphosis: A Trigger or an Association?” (page unavailable), the paper says JH decline activates TcE93 at later larval stages and proposes an additional competence factor governing when TcE93 can be induced. But it says threshold size is associated with JH decline, not that crossing the threshold causes it; the trigger of the normal JH decline remains unknown. It also does not characterize the additional factor as necessary specifically for “broad” induction. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe best candidates for the signal needed for broad induction are myoglianin and/or ecdysteroids.
“The best candidates are myoglianin and/or ecdysteroids [9,8].”
From Regulation of metamorphosis in holometabolous insects (2026) · cites this paper as [9]
The Introduction (page not available in our copy) says that ecdysone induces Broad complex (Br-C) expression in the absence of juvenile hormone, supporting ecdysteroids as a candidate signal. It does not mention myoglianin or identify these as the best candidates for Broad induction. (LLM, conf=0.84)
Experimental — accuracy not yet measured
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Research works printed but not linked: 11
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Cited by
Sorted by citations
Truman, J. W., & Riddiford, L. M. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2201071119 · Cited by 53 · see citing works
He, L. L., Shin, S. H., Wang, Z., Yuan, I., Weschler, R., Chiou, A., Koyama, T., Nijhout, H. F., & Suzuki, Y. (2020) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2020.103452 · Cited by 53 · see citing works
Chafino, S., Giannios, P., Casanova, J., Martín, D., & Franch-Marro, X. (2023) · eLife · doi:10.7554/elife.84648 · Cited by 30 · see citing works
Self-citationRegulation of metamorphosis in holometabolous insects
Truman, J. W., & Riddiford, L. M. (2026) · Current Opinion in Insect Science · doi:10.1016/j.cois.2026.101508 · Cited by 6 · see citing works
- Authors
- Chafino, S., Ureña, E., Casanova, J., Casacuberta, E., Franch-Marro, X., & Martín, D.
- Affiliations
- Universitat Pompeu Fabra (ES)
- Consejo Superior de Investigaciones Científicas (ES)
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 27
- Issue
- 4
- Pages
- 1039-1049.e2
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2941553397
- Cited by
- 89
- References
- 0
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 18 · 2023: 12 · 2022: 9 · 2021: 12 · 2020: 14 · 2019: 6
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by-nc-nd)
- Funders
- Agència de Gestió d’Ajuts Universitaris i de Recerca
- Ministerio de Economía y Competitividad
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Insect Resistance and Genetics
- Keywords
- Tribolium castaneum, threshold size, Kr-h1, body size regulation, holometabolous insects, last instar larva, gene expression regulation
- MeSH terms
- Animals, Larva, Metamorphosis, Biological, Tribolium, Up-Regulation, Insect Proteins, Body Size
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