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Intercellular bridges are essential for transposon repression and meiosis in the male germline

Julia Sorkin, Kevin Tilton, Matthew A. Lawlor, Shreya N. Sarathy, Shun Liang, Angelina Albanese, Mashiat Rabbani, Saher S. Hammoud, Christopher E. Ellison, Florencia Pratto and Devanshi Jain (devanshi.jain@rutgers.edu)
Additional contact information
Julia Sorkin: Rutgers University
Kevin Tilton: Rutgers University
Matthew A. Lawlor: Rutgers University
Shreya N. Sarathy: Rutgers University
Shun Liang: Rutgers University
Angelina Albanese: Rutgers University
Mashiat Rabbani: University of Michigan
Saher S. Hammoud: University of Michigan
Christopher E. Ellison: Rutgers University
Florencia Pratto: NIH
Devanshi Jain: Rutgers University

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract Germ cell connectivity via intercellular bridges is a widely conserved feature across metazoans. However, its functional significance is poorly understood. Intercellular bridges are essential for fertility in male mice as genetic ablation of a critical bridge component, TEX14, causes spermatogenic failure, but the underlying reasons are unknown. Here we utilized a Tex14 hypomorph with reduced intercellular bridges along with Tex14-null mice that completely lack bridges to examine the roles of germ cell connectivity during spermatogenesis. We report that in males deficient for TEX14 and intercellular bridges, germ cells fail to complete meiotic DNA replication, synapsis and meiotic double-strand break repair. They also derepress retrotransposons and accumulate retrotransposon-encoded proteins during meiosis. Single-cell RNA-sequencing confirms sharing of transcripts between wild-type spermatids and demonstrates its partial attenuation in Tex14 hypomorphs, indicating that intercellular bridges enable cytoplasmic exchange between connected germ cells in testes. Our findings suggest that regulation of meiosis is non-cell-intrinsic and inform a model in which intercellular bridges influence critical meiotic events and protect germline genome integrity during spermatogenesis.

Date: 2025
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DOI: 10.1038/s41467-025-56742-9

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