Title

Mouse EWSR1 is crucial for spermatid post-meiotic transcription and spermiogenesis.

Document Type

Article

Publication Date

6-1-2021

Publication Title

Development (Cambridge, England)

Keywords

JMG

JAX Source

Development 2021 Jun; 148(11):dev199414

Volume

148

Issue

11

ISSN

1477-9129

PMID

34100066

DOI

https://doi.org/10.1242/dev.199414

Grant

GM078452, GM076458, CA034196

Abstract

Spermatogenesis is precisely controlled by complex gene-expression programs. During mammalian male germ-cell development, a crucial feature is the repression of transcription before spermatid elongation. Previously, we discovered that the RNA-binding protein EWSR1 plays an important role in meiotic recombination in mouse, and showed that EWSR1 is highly expressed in late meiotic cells and post-meiotic cells. Here, we used an Ewsr1 pachytene stage-specific knockout mouse model to study the roles of Ewsr1 in late meiotic prophase I and in spermatozoa maturation. We show that loss of EWSR1 in late meiotic prophase I does not affect proper meiosis completion, but does result in defective spermatid elongation and chromocenter formation in the developing germ cells. As a result, male mice lacking EWSR1 after pachynema are sterile. We found that, in Ewsr1 CKO round spermatids, transition from a meiotic gene-expression program to a post-meiotic and spermatid gene expression program related to DNA condensation is impaired, suggesting that EWSR1 plays an important role in regulation of spermiogenesis-related mRNA synthesis necessary for spermatid differentiation into mature sperm.

Comments

We thank Tim Billings for technical help and Mary Ann Handel for critical reading of the manuscript. This article is dedicated to the memory of Ken Paigen, an excellent colleague, mentor and visionary.

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