PUBLICATION
Gag proteins encoded by endogenous retroviruses are required for zebrafish development
- Authors
- Chang, N.C., Wells, J.N., Wang, A.Y., Schofield, P., Huang, Y.C., Truong, V.H., Simoes-Costa, M., Feschotte, C.
- ID
- ZDB-PUB-250429-9
- Date
- 2025
- Source
- Proceedings of the National Academy of Sciences of the United States of America 122: e2411446122e2411446122 (Journal)
- Registered Authors
- Keywords
- addiction, cooperation, embryogenesis, transposable elements, zebrafish
- MeSH Terms
-
- DNA Transposable Elements/genetics
- Chick Embryo
- Gene Products, gag*/genetics
- Gene Products, gag*/metabolism
- Embryonic Development/genetics
- Gene Expression Regulation, Developmental
- Animals
- Endogenous Retroviruses*/genetics
- Endogenous Retroviruses*/metabolism
- Embryo, Nonmammalian
- Neural Crest/embryology
- Neural Crest/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Cell Movement
- Mesoderm/embryology
- Mesoderm/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 40294259 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Chang, N.C., Wells, J.N., Wang, A.Y., Schofield, P., Huang, Y.C., Truong, V.H., Simoes-Costa, M., Feschotte, C. (2025) Gag proteins encoded by endogenous retroviruses are required for zebrafish development. Proceedings of the National Academy of Sciences of the United States of America. 122:e2411446122e2411446122.
Abstract
Transposable elements (TEs) make up the bulk of eukaryotic genomes and examples abound of TE-derived sequences repurposed for organismal function. The process by which TEs become coopted remains obscure because most cases involve ancient, transpositionally inactive elements. Reports of active TEs serving beneficial functions are scarce and often contentious due to difficulties in manipulating repetitive sequences. Here, we show that recently active TEs in zebrafish encode products critical for embryonic development. Knockdown and rescue experiments demonstrate that the endogenous retrovirus family BHIKHARI-1 (Bik-1) encodes a Gag protein essential for mesoderm development. Mechanistically, Bik-1 Gag associates with the cell membrane, and its ectopic expression in chicken embryos alters cell migration. Similarly, depletion of BHIKHARI-2 Gag, a relative of Bik-1, causes defects in neural crest development in zebrafish. We propose an "addiction" model to explain how active TEs can be integrated into conserved developmental processes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping