We aim to elucidate molecular mechanisms involved in several developmental processes. Major targets are mesoderm tissues and germ cell development; sexual fate decision, spermatogenesis and oogeneis. We like to understand mechanisms how germ cells chose two alternative pathways to form sperm or oocyte. For the functional analyses, we use Cas9-mediated gene editing technology to facilitate mutant mouse production.
(A) Nanos2 proteins (green) are localized in the P-bodies in cytoplasm of embryonic male germ cells (red).
(B) A section of ovary at one day after birth (P1). Germ cells (red) are enclosed by granulosa cells (green), thereby oocyte maturation is promoted.
(C) A model for sex determination of germ cells. In ovary, RA and BMP signaling act on germ cells to direct female pathway. If those pathways are disrupted by STRA8/ SMAD4-dKO, germ cells enter to male pathway.
(D) Sex reversal of germ cells induced by disrupting RA signaling in SMAD4-KO ovary, in which NANOS2 expression (red) was induced even in the ovary. FOXL2 (blue) is a marker for female somatic cells. TRA98 (green)is a germ cell marker.
Zhou, Z., Kawabe, H., Suzuki, A., Shinmyozu, K., and Saga, Y. (2017). NEDD4 controls spermatogonial stem cell homeostasis and stress response by regulating messenger ribonucleoprotein complexes. Nat Commun 8, 15662.
Wu, Q., Fukuda, K., Kato, Y., Zhou, Z., Deng, C.X., and Saga, Y. (2016). Sexual fate change of XX germ cells caused by the deletion of SMAD4 and STRA8 independent of somatic sex reprogramming. PLoS Biol 14, e1002553.
Kato, Y., Katsuki, T., Kokubo, H., Masuda, A., and Saga, Y. (2016). Dazl is a target RNA suppressed by mammalian NANOS2 in sexually differentiating male germ cells. Nat Commun 7, 11272.