Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain
| Autor: | Akira Shibuya, Satomi Kanno, Masafumi Muratani, Mikio Hoshino, Yukiko Ishikawa, Yoshiya Kawaguchi, Yousuke Tsuneoka, Masashi Yanagisawa, Mariko Yamashita, Hiromasa Funato, Mark A. Magnuson, Tomoo Owa, Yuchio Yanagawa, Yo-ichi Nabeshima, Tomoyuki Fujiyama, Miyo Kakizaki, Kazumasa Kanemaru, Mai Nagaoka, Satoshi Miyashita |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine endocrine system medicine.medical_specialty Sex Differentiation Period (gene) sexual differentiation Biology General Biochemistry Genetics and Molecular Biology kisspeptin Sexual Behavior Animal 03 medical and health sciences Prosencephalon sexual behavior 0302 clinical medicine Internal medicine medicine Animals Cell Lineage hypothalamus Gonads lcsh:QH301-705.5 Mice Knockout Ptf1a Third ventricle Sexual differentiation Gene Expression Regulation Developmental Embryo Mammalian central nervous system Phenotype Mice Inbred C57BL Neuroepithelial cell 030104 developmental biology medicine.anatomical_structure Endocrinology nervous system lcsh:Biology (General) Hypothalamus Forebrain Female Abnormality 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Cell Reports, Vol 24, Iss 1, Pp 79-94 (2018) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2018.06.010 |
| Popis: | Summary: 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: sexual differentiation, sexual behavior, hypothalamus, Ptf1a, kisspeptin, central nervous system |
| Databáze: | OpenAIRE |
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