# A muscle-centered hierarchical breakdown underlies flight loss during silkworm domestication

**Authors:** Rongpeng Liu, Chen Zhao, Jie Hu, Yongbing Ba, Yiting Ran, Yuanyuan Mu, Yiyun Tang, Yan Ma, Zhiming Zhang, Kaiqi Guo, Keshu Dong, Xiao Li, Yumeng Zhu, Wei Tan, Hanfu Xu

PMC · DOI: 10.1016/j.isci.2026.114846 · iScience · 2026-01-29

## TL;DR

The study shows how silkworms lost flight through muscle-related genetic changes, offering insights into pest control.

## Contribution

The paper identifies a conserved, muscle-centered genetic module responsible for flight loss in Lepidoptera.

## Key findings

- Flight loss in Bombyx mori is due to a breakdown in flight muscle cells and energy production.
- Disruption of the Yki gene worsens wing defects in Bombyx mori.
- The same genetic module is conserved in Helicoverpa armigera, suggesting a target for pest control.

## Abstract

Recurrent loss of complex traits such as insect flight offers insights into evolutionary regression, as seen in Bombyx mori domestication from its flight-capable ancestor B. mandarina. By integrating single-cell and spatial transcriptomics of developing flight organs in both Bombyx species, we reveal that flight loss occurs through a coordinated breakdown centered on flight muscle cells. This stems from disintegration of a multi-tiered genetic module with three interconnected components: failures in mitochondrial energy production (e.g., COX3/ND1), wing vein patterning (involving Dally/CtBP), and flight muscle specification (controlled by Yki). Knocking down key components in B. mandarina induced flightlessness, and perturbing the Hippo effector Yki in B. mori exacerbated wing defects, together highlighting the pathway’s dosage-sensitive nature. Notably, this muscle-centric module is conserved in the migratory pest Helicoverpa armigera, where its disruption similarly impaired flight. Our work establishes trait degeneration as a muscle-centered collapse and identifies a conserved target for precision pest control.

•Single-cell and spatial atlas reveals a muscle-centric basis for flight loss in Lepidoptera•Flight degeneration follows hierarchical disintegration of a three-tiered genetic module•Conserved flight module in Helicoverpa armigera informs precision pest control

Single-cell and spatial atlas reveals a muscle-centric basis for flight loss in Lepidoptera

Flight degeneration follows hierarchical disintegration of a three-tiered genetic module

Conserved flight module in Helicoverpa armigera informs precision pest control

Entomology; Molecular biology; Evolutionary biology; Transcriptomics

## Linked entities

- **Genes:** COX3 (cytochrome c oxidase subunit III) [NCBI Gene 4514], ND1 (NADH dehydrogenase subunit 1) [NCBI Gene 4535], dally (division abnormally delayed) [NCBI Gene 39013], CtBP (C-terminal Binding Protein) [NCBI Gene 41602], YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413]
- **Species:** Bombyx mori (taxon 7091), Helicoverpa armigera (taxon 29058)

## Full-text entities

- **Genes:** ND1 [NCBI Gene 804653], fln [NCBI Gene 100192380], LOC101738867 [NCBI Gene 101738867], ND5 [NCBI Gene 809258], Notch [NCBI Gene 692561], ND1 [NCBI Gene 809263], COX3 [NCBI Gene 804644], LOC101743162 [NCBI Gene 101743162], LOC101738228 [NCBI Gene 101738228], Fng [NCBI Gene 100144549], ND4 [NCBI Gene 809259], Rps9 [NCBI Gene 692718], COX1 [NCBI Gene 809266], Kettin (kettin protein) [NCBI Gene 692378] {aka Bmkettin}, COX3 [NCBI Gene 4266952], ND4L [NCBI Gene 804646], LOC101740813 [NCBI Gene 101740813], Gata-beta [NCBI Gene 693014]
- **Diseases:** mitochondrial deficits (MESH:D028361), flight (MESH:C000722495), wing defects (MESH:D008579), flight degeneration (MESH:D009410), muscle cell dysfunction (MESH:D009135)
- **Chemicals:** gold (MESH:D006046), OCT (MESH:C051883), H&amp;E (MESH:D006371), ATP (MESH:D000255), PBS (MESH:D007854)
- **Species:** Bombyx mandarina (wild silkworm, species) [taxon 7092], Bombyx (genus) [taxon 7090], Mandarina (genus) [taxon 83227], Homo sapiens (human, species) [taxon 9606], Helicoverpa armigera (American bollworm, species) [taxon 29058], Bombyx mori (domestic silkworm, species) [taxon 7091], Drosophila melanogaster (fruit fly, species) [taxon 7227]
- **Mutations:** C-28 C, S10D

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12915254/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12915254/full.md

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Source: https://tomesphere.com/paper/PMC12915254