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
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Embryonic Development/genetics
  • Endogenous Retroviruses*/genetics
  • Endogenous Retroviruses*/metabolism
  • Cell Movement
  • DNA Transposable Elements/genetics
  • Embryo, Nonmammalian
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Neural Crest/embryology
  • Neural Crest/metabolism
  • Gene Expression Regulation, Developmental
  • Chick Embryo
  • Mesoderm/embryology
  • Mesoderm/metabolism
  • Animals
  • Gene Products, gag*/genetics
  • Gene Products, gag*/metabolism
PubMed
40294259 Full text @ Proc. Natl. Acad. Sci. USA
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
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping