Opposing effects of retinoic acid and FGF9 on Nanos2 expression and meiotic entry of mouse germ cells.
In the mouse, three genes that are homologous to the Drosophila Nanos (Nos) gene have been identified. Deletion of one of these genes, Nanos2, results in male sterility, owing to loss of germ cells during fetal life. Before apoptosis, Nanos2-null gonocytes enter meiosis, suggesting that Nanos2 functions as a meiotic repressor. Here, we show that Nanos2 is continuously expressed in male germ cells from fetal gonocytes to postnatal spermatogonial stem cells. We observed that the promeiotic factor AtRA, an analog of retinoic acid (RA), downregulates NANOS2 levels, in both fetal and postnatal gonocytes, while promoting meiosis. Interestingly, FGF9, a growth factor crucial for sex differentiation and survival of fetal gonocytes, upregulates levels of NANOS2 in both male and female primordial germ cells (PGCs) and in premeiotic spermatogonia. This effect was paralleled by an impairment of meiotic entry, suggesting that FGF9 acts as an inhibitor of meiosis through the upregulation of Nanos2. We found that NANOS2 interacts with PUM2, and that these two proteins colocalize in the ribonucleoparticle and polysomal fractions on sucrose gradients, supporting the notion that they bind RNA. Finally, we found that recombinant NANOS2 binds to two spermatogonial mRNAs, Gata2 and Taf7l, which are involved in germ-cell differentiation.
Department of Public Health and Cellular Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
Florencia
F
Barrios
Doria
D
Filipponi
Manuela
M
Pellegrini
Maria Paola
MP
Paronetto
Sara
S
Di Siena
Raffaele
R
Geremia
Pellegrino
P
Rossi
Massimo
M
De Felici
Emmanuele A
EA
Jannini
Susanna
S
Dolci
D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051525:Fibroblast Growth Factor 9 / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005854:Germ Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D010063:Ovum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000378:metabolism; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D002352:Carrier Proteins; D051525:Fibroblast Growth Factor 9; C477341:Nanos2 protein, mouse; C445087:Pum2 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D014212:Tretinoin