Wei-Fang ChangJie XuTzu-Ying LinJing HsuHsiu-Mei Hsieh-LYuh-Ming HwuJi-Long LiuChung-Hao LuLI-YING SUNG2020-04-212020-04-212020https://scholars.lib.ntu.edu.tw/handle/123456789/485177The defective human survival motor neuron 1 (SMN1) gene leads to spinal muscular atrophy (SMA), the most common genetic cause of infant mortality. We previously reported that loss of SMN results in rapid differentiation of Drosophila germline stem cells and mouse embryonic stem cells (ESCs), indicating that SMN also plays important roles in germ cell development and stem cell biology. Here, we show that in healthy mice, SMN is highly expressed in the gonadal tissues, prepubertal spermatogonia, and adult spermatocytes, whereas low SMN expression is found in differentiated spermatid and sperm. In SMA-like mice, the growth of testis tissues is retarded, accompanied with gamete development abnormalities and loss of the spermatogonia-specific marker. Consistently, knockdown of Smn1 in spermatogonial stem cells (SSCs) leads to a compromised regeneration capacity in vitro and in vivo in transplantation experiments. In SMA-like mice, apoptosis and accumulation of the R-loop structure were significantly elevated, indicating that SMN plays a critical role in the survival of male germ cells. The present work demonstrates that SMN, in addition to its critical roles in neuronal development, participates in mouse germ cell and spermatogonium maintenance. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.Gametogenesis; SMN; Spermatogonium[SDGs]SDG3survival motor neuron protein 1; survival motor neuron protein 1; adult; animal cell; animal experiment; animal tissue; apoptosis; Article; cell self-renewal; cell survival; controlled study; embryo; female; fluorescence activated cell sorting; gametogenesis; germ cell; in vitro study; in vivo study; male; mouse; nerve cell differentiation; nonhuman; prepuberty; protein analysis; protein depletion; protein expression; protein function; sperm; spermatid; spermatocyte; spermatogonium; testis development; tissue regeneration; tissue transplantation; animal; cell culture; cell differentiation; cytology; gene expression regulation; genetics; metabolism; signal transduction; spermatogenesis; spermatogonium; stem cell; testis; Animals; Cell Differentiation; Cell Self Renewal; Cell Survival; Cells, Cultured; Gene Expression Regulation, Developmental; Male; Mice; Signal Transduction; Spermatogenesis; Spermatogonia; Stem Cells; Survival of Motor Neuron 1 Protein; Testisjournal article10.3390/ijms21030794