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PreprintCC BYbioRxiv

Lost and found: beer belly is a novel, ancient regulator of animal development

2 more authors
  1. 1Durham University

Abstract

Single-cell RNA sequencing (scRNA-seq) can provide new insights into the regulation of developmental processes by revealing unknown or overlooked genes. We identified a novel gene called beer belly (bebe) as a marker of a segment addition zone (SAZ) associated cell cluster in a single-cell atlas of the spider Parasteatoda tepidariorum. Here we show that bebe is an ancient toolkit gene encoding a previously uncharacterised protein predicted to be secreted, which likely plays an important role in the development of most animal phyla. However, we could not identify a bebe ortholog in any mammal or holometabolous insect, suggesting it has been lost in these lineages and explaining why it has been overlooked to date. Knock-down of bebe expression in P. tepidariorum demonstrates that it regulates SAZ size and consequently segment size by interacting with Wnt8. Our findings also suggest that bebe may regulate segmentation in other invertebrates and play additional developmental roles in bilaterian and non-bilaterian animals, likely ancestrally, through modulation of Wnt signalling. This study emphasises the promise of applying single-cell sequencing across a diverse range of species to better understand the regulation of development beyond candidate genes from traditional models, allowing us to better characterise the animal developmental toolkit and its evolution.

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BibTeX
@misc{schultz2026lost,
  title = {{Lost and found: beer belly is a novel, ancient regulator of animal development}},
  author = {Z. X. Schultz and G. Blakeley and M. E. Aase-Remedios and D. V. Grillmayer and D. J. Leite and T. Frankish and G. Sutton and G. Genikhovich and S. Scholpp and M. Pechmann and J. M. Martin-Duran and N. Turetzek and R. Janssen and A. P. McGregor},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.24.761492},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.24.761492v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Lost and found: beer belly is a novel, ancient regulator of animal development
AU  - Z. X. Schultz
AU  - G. Blakeley
AU  - M. E. Aase-Remedios
AU  - D. V. Grillmayer
AU  - D. J. Leite
AU  - T. Frankish
AU  - G. Sutton
AU  - G. Genikhovich
AU  - S. Scholpp
AU  - M. Pechmann
AU  - J. M. Martin-Duran
AU  - N. Turetzek
AU  - R. Janssen
AU  - A. P. McGregor
PY  - 2026
DA  - 2026/10/24
PB  - bioRxiv
DO  - 10.64898/2026.10.24.761492
UR  - https://www.biorxiv.org/content/10.64898/2026.10.24.761492v1
AB  - Single-cell RNA sequencing (scRNA-seq) can provide new insights into the regulation of developmental processes by revealing unknown or overlooked genes. We identified a novel gene called beer belly (bebe) as a marker of a segment addition zone (SAZ) associated cell cluster in a single-cell atlas of the spider Parasteatoda tepidariorum. Here we show that bebe is an ancient toolkit gene encoding a previously uncharacterised protein predicted to be secreted, which likely plays an important role in the development of most animal phyla. However, we could not identify a bebe ortholog in any mammal or holometabolous insect, suggesting it has been lost in these lineages and explaining why it has been overlooked to date. Knock-down of bebe expression in P. tepidariorum demonstrates that it regulates SAZ size and consequently segment size by interacting with Wnt8. Our findings also suggest that bebe may regulate segmentation in other invertebrates and play additional developmental roles in bilaterian and non-bilaterian animals, likely ancestrally, through modulation of Wnt signalling. This study emphasises the promise of applying single-cell sequencing across a diverse range of species to better understand the regulation of development beyond candidate genes from traditional models, allowing us to better characterise the animal developmental toolkit and its evolution.
ER  -