Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain
Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain
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DOI：
10.1016/j.celrep.2018.06.010
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发表时间：
2018-07-03
期刊：
影响因子：
8.8
通讯作者：
Hoshino, Mikio
中科院分区：
文献类型：
--
作者：
Fujiyama, Tomoyuki;Miyashita, Satoshi;Hoshino, Mikio
哺乳动物的大脑在围产期的关键时期经历性分化的性腺激素。然而，早期阶段的机制尚未得到很好的研究。我们发现Ptf1a在第三脑室周围的某些神经上皮细胞和未成熟神经元中表达，这些神经元在几个下丘脑核团中产生各种神经元。我们发现，条件性Ptf1a缺陷小鼠（Ptf1a cKO）表现出异常的性别偏见的行为和生殖器官在两种性别。对性腺切除的动物给予性腺激素显示，异常行为是由被敲除的大脑的紊乱的性发育引起的。因此，cKO下丘脑中性别偏向基因的表达严重改变。特别是，Kiss1，重要的性别分化的大脑，是急剧减少cKO下丘脑，这可能有助于观察到的表型在Ptf1a cKO。这些结果表明，前脑Ptf1a是最早的调节性分化的大脑。
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.