Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain

Tomoyuki Fujiyama, Satoshi Miyashita, Yousuke Tsuneoka, Kazumasa Kanemaru, Miyo Kakizaki, Satomi Kanno, Yukiko Ishikawa, Mariko Yamashita, Tomoo Owa, Mai Nagaoka, Yoshiya Kawaguchi, Yuchio Yanagawa, Mark A. Magnuson, Masafumi Muratani, Akira Shibuya, Yo ichi Nabeshima, Masashi Yanagisawa, Hiromasa Funato, Mikio Hoshino

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)79-94
Number of pages16
JournalCell Reports
Volume24
Issue number1
DOIs
StatePublished - Jul 3 2018

Keywords

  • Ptf1a
  • central nervous system
  • hypothalamus
  • kisspeptin
  • sexual behavior
  • sexual differentiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain'. Together they form a unique fingerprint.

  • Cite this

    Fujiyama, T., Miyashita, S., Tsuneoka, Y., Kanemaru, K., Kakizaki, M., Kanno, S., Ishikawa, Y., Yamashita, M., Owa, T., Nagaoka, M., Kawaguchi, Y., Yanagawa, Y., Magnuson, M. A., Muratani, M., Shibuya, A., Nabeshima, Y. I., Yanagisawa, M., Funato, H., & Hoshino, M. (2018). Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain. Cell Reports, 24(1), 79-94. https://doi.org/10.1016/j.celrep.2018.06.010