Gonocytes-to-spermatogonia transition initiates prior to birth in murine testes and it requires FGF signaling.
Spermatogenesis is a continuous and highly coordinated process of spermatozoa production. In mice, this process is believed to initiate shortly after birth with the emergence of nascent spermatogonia in the testes. However, because the nascent spermatogonia originated from the gonocytes are morphologically indistinguishable from their predecessors and there is no clear definition for the gonocytes-to-spermatogonia transition (GST), it remains unclear when and how spermatogenesis is initiated in the mouse testes. To address these questions, we characterized the emergence of nascent spermatogonia in ICR mice. We found that GST is initiated in a subset of gonocytes as early as E18.5. These nascent spermatogonia express markers typical of undifferentiated spermatogonia residing in testes of adult mice. In addition to markers expression, we identified FOXO1 nuclear-to-cytoplasmic translocation as a novel feature of GST distinguishing nascent spermatogonia from the gonocytes. Using those criteria, we demonstrated that GST requires FGF signaling. When FGF signaling was inhibited pharmacologically, gonocytes retained nuclear FOXO1 expression, did not express spermatogonial markers and failed to proliferate. We found that FGF signaling acts upstream of GDNF and RA signalings for the activation of the MEK/ERK and PI3K/Akt pathways in germ cells during GST. Taken together, we defined the precise timing of GST and revealed FGF signaling as a master regulator of GST in the perinatal mouse testes.
Department of Genetics, The Graduate University for Advanced studies, 1111 Yata, Mishima, 411-8540, Shizuoka, Japan; Division of Mammalian Development, National Institute of Genetics, 1111 Yata, Mishima, 411-8540, Shizuoka, Japan.
Han Pin
HP
Pui
Department of Genetics, The Graduate University for Advanced studies, 1111 Yata, Mishima, 411-8540, Shizuoka, Japan; Division of Mammalian Development, National Institute of Genetics, 1111 Yata, Mishima, 411-8540, Shizuoka, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan. Electronic address: ysaga@nig.ac.jp.
Yumiko
Y
Saga
D000818:Animals; D002454:Cell Differentiation; D005346:Fibroblast Growth Factors / Q000502:physiology*; D000071161:Forkhead Box Protein O1 / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000502:physiology; D020935:MAP Kinase Signaling System; D008297:Male; D008813:Mice, Inbred ICR; D013091:Spermatogenesis; D013093:Spermatogonia / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000196:embryology; D046509:Tissue Culture Techniques; D059467:Transcriptome; D014212:Tretinoin / Q000502:physiology
D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D014212:Tretinoin; D005346:Fibroblast Growth Factors
Differentiating spermatogonia; FGF signaling; FOXO1; Gonocytes; Spermatogonial stem cells; Transition