@article{771eaa91859a415fa0ed896e822715f0,
title = "Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain",
abstract = "The mammalian brain undergoes sexual differentiation by gonadal hormones during the perinatal critical period. However, the machinery at earlier stages has not been well studied. We found that Ptf1a is expressed in certain neuroepithelial cells and immature neurons around the third ventricle that give rise to various neurons in several hypothalamic nuclei. We show that conditional Ptf1a-deficient mice (Ptf1a cKO) exhibit abnormalities in sex-biased behaviors and reproductive organs in both sexes. Gonadal hormone administration to gonadectomized animals revealed that the abnormal behavior is caused by disorganized sexual development of the knockout brain. Accordingly, expression of sex-biased genes was severely altered in the cKO hypothalamus. In particular, Kiss1, important for sexual differentiation of the brain, was drastically reduced in the cKO hypothalamus, which may contribute to the observed phenotypes in the Ptf1a cKO. These findings suggest that forebrain Ptf1a is one of the earliest regulators for sexual differentiation of the brain. Fujiyama et al. find that forebrain-specific Ptf1a-deficient mice (Ptf1a cKO) exhibit abnormalities in sexually dimorphic behaviors, reproductive organs, and severely altered expression of sex-biased genes, including Kiss1, in the hypothalamus in both sexes, which suggests that forebrain Ptf1a is one of the earliest regulators for sexual differentiation of the brain.",
keywords = "Ptf1a, central nervous system, hypothalamus, kisspeptin, sexual behavior, sexual differentiation",
author = "Tomoyuki Fujiyama and Satoshi Miyashita and Yousuke Tsuneoka and Kazumasa Kanemaru and Miyo Kakizaki and Satomi Kanno and Yukiko Ishikawa and Mariko Yamashita and Tomoo Owa and Mai Nagaoka and Yoshiya Kawaguchi and Yuchio Yanagawa and Magnuson, {Mark A.} and Masafumi Muratani and Akira Shibuya and Nabeshima, {Yo ichi} and Masashi Yanagisawa and Hiromasa Funato and Mikio Hoshino",
note = "Funding Information: We thank all Hoshino and Y/F lab members for kind support and technical assistance. We are also grateful to Dr. Ruth Yu for her comments; Drs. T. Tanaka, A. Imura, M. Watanabe, T. Shimogori, Y. Sasai, and M. Matsuda for critical suggestions and antibody reagents; and Drs. K. Takase and T. Terashima for helpful advice on histology. M. Yanagisawa was an investigator at the Howard Hughes Medical Institute (HHMI) during the period of this work. This work is supported by Grant-in-Aid for Research Activity Start-Up (24800088 to T.F.), Japan Society for the Promotion of Science (JSPS) Fellows (15J00393 to T.F.), JSPS KAKENHI (26220207 and 17H06095 to M. Yanagisawa and H.F.; 17H04023, 16K15187, and 15H05942 to H.F.), CREST (JPMJCR1655 to M. Yanagisawa), Scientific Research (15H04268 to M.H.), the Funding Program for World-Leading Innovative R&D on Science and Technology (to M. Yanagisawa) from the JSPS, the Strategic Research Program for Brain Sciences (SRPBS) (17dm0107085h0002 to M.H.) of the Japan Agency for Medical Research and Development (AMED), Intramural Research Grants for Neurological and Psychiatric Disorders of the National Center of Neurology and Psychology (NCNP) (27-7, 28-4 to M.H.), Innovative Areas (15H01304, 16H06528 to M.H.; 17H05963 to Y.T.), and World Premier International Research Center Initiative (to M. Yanagisawa) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. Funding Information: We thank all Hoshino and Y/F lab members for kind support and technical assistance. We are also grateful to Dr. Ruth Yu for her comments; Drs. T. Tanaka, A. Imura, M. Watanabe, T. Shimogori, Y. Sasai, and M. Matsuda for critical suggestions and antibody reagents; and Drs. K. Takase and T. Terashima for helpful advice on histology. M. Yanagisawa was an investigator at the Howard Hughes Medical Institute (HHMI) during the period of this work. This work is supported by Grant-in-Aid for Research Activity Start-Up ( 24800088 to T.F.), Japan Society for the Promotion of Science (JSPS) Fellows ( 15J00393 to T.F.), JSPS KAKENHI ( 26220207 and 17H06095 to M. Yanagisawa and H.F.; 17H04023 , 16K15187 , and 15H05942 to H.F.), CREST ( JPMJCR1655 to M. Yanagisawa), Scientific Research ( 15H04268 to M.H.), the Funding Program for World-Leading Innovative R&D on Science and Technology (to M. Yanagisawa) from the JSPS , the Strategic Research Program for Brain Sciences (SRPBS) ( 17dm0107085h0002 to M.H.) of the Japan Agency for Medical Research and Development (AMED) , Intramural Research Grants for Neurological and Psychiatric Disorders of the National Center of Neurology and Psychology (NCNP) ( 27-7 , 28-4 to M.H.), Innovative Areas ( 15H01304 , 16H06528 to M.H.; 17H05963 to Y.T.), and World Premier International Research Center Initiative (to M. Yanagisawa) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2018",
month = jul,
day = "3",
doi = "10.1016/j.celrep.2018.06.010",
language = "English (US)",
volume = "24",
pages = "79--94",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}