DDX20 is required for cell-cycle reentry of prospermatogonia and establishment of spermatogonial stem cell pool during testicular development in mice
Dingfeng Zou 1, Kai Li 1, Luying Su 1, Jun
Liu 1, Yan Lu 1, Rong Huang 1, Mengzhen Li 1, Xinyu Mang 1, Qi Geng 1, Pengyu
Li 1, Jielin Tang 1, Zhixin Yu 1, Zexuan Zhang 1, Dingyao Chen 1, Shiying Miao
1, Jia Yu 2, Wei Yan 3, Wei Song 4
Dev Cell. 2024 Apr
22:S1534-5807(24)00227-2. doi: 10.1016/j.devcel.2024.04.002.
PMID: 38657611
Abstract
RNA-binding proteins (RBPs), as key
regulators of mRNA fate, are abundantly expressed in the testis. However, RBPs
associated with human male infertility remain largely unknown. Through
bioinformatic analyses, we identified 62 such RBPs, including an evolutionarily
conserved RBP, DEAD-box helicase 20 (DDX20). Male germ-cell-specific
inactivation of Ddx20 at E15.5 caused T1-propsermatogonia (T1-ProSG) to fail to
reenter cell cycle during the first week of testicular development in mice. Consequently,
neither the foundational spermatogonial stem cell (SSC) pool nor progenitor
spermatogonia were ever formed in the knockout testes. Mechanistically, DDX20
functions to control the translation of its target mRNAs, many of which encode
cell-cycle-related regulators, by interacting with key components of the
translational machinery in prospermatogonia. Our data demonstrate a previously
unreported function of DDX20 as a translational regulator of critical
cell-cycle-related genes, which is essential for cell-cycle reentry of T1-ProSG
and formation of the SSC pool.