A genetic analysis of hypothalamic development and function using Ptf1a-genetically modified mice.

使用 Ptf1a 转基因小鼠对下丘脑发育和功能进行遗传分析。

• 批准号: 24800088
• 负责人: FUJIYAMA Tomoyuki
• 金额: $ 1.91万
• 依托单位: University of Tsukuba (2013)独立行政法人国立精神・神経医療研究センター (2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-08-31 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24800088/
• 关键词: 神経発生; 視床下部; マウス; エネルギー消費; Ptf1a; 神経上皮; 遺伝学; エネルギーバランス; Nkx2.1; GnRH; 発生生物学; 肥満; 摂食

Ptf1a, a bHLH-transcription factor, is known to be essential for the development of mammalian pancreas. Several groups and we have reported involvement of Ptf1a in neuron subtype specification in CNS regions. Here we report Ptf1a expression in the developing hypothalamus.Hypothalamus is involved in the regulation of homeostasis; however, developmental mechanism and function of hypothalamic neurons remain to be understood. During development, we found Ptf1a was expressed in a part of diencephalic neuroepithelium, that is, a source of hypothalamic neurons. Using the Cre/loxP system, we identified many "Ptf1a lineage cells" in the several ventral hypothalamic nucleus. Conditional knockout (cKO) of this gene in the developing hypothalamus resulted in late-onset obesity caused by lower activity, and infertility. The present results suggest that Ptf1a in diencephalon is required for the normal development of function of hypothalamic neurons and the metabolic control, including body weight.

Ptf1a是一种bhlh转录因子，已知对哺乳动物胰腺的发育至关重要。几个研究小组和我们已经报道了Ptf1a参与中枢神经系统区域的神经元亚型规范。在这里，我们报道了Ptf1a在发育中的下丘脑中的表达。下丘脑参与调节体内平衡；然而，下丘脑神经元的发育机制和功能尚不清楚。在发育过程中，我们发现Ptf1a在间脑神经上皮的一部分中表达，即下丘脑神经元的来源。使用Cre/loxP系统，我们在几个下丘脑腹侧核中鉴定了许多“Ptf1a谱系细胞”。发育中的下丘脑中该基因的条件敲除（cKO）导致活动减少引起的迟发性肥胖和不孕。目前的研究结果表明，间脑Ptf1a是下丘脑神经元功能正常发育和代谢控制（包括体重控制）所必需的。

项目成果

Ptf1a遺伝子改変マウスを用いた視床下部の発生および機能の解析

使用 Ptf1a 基因修饰小鼠分析下丘脑发育和功能

• 发表时间: 2012
• 作者: Seto Y;Nakatani T;Masuyama N;Minaki Y;Kumai M;Hamaguchi A;Kawaguchi Y;Ikenaka K;Takebayashi H;Ishiwata S;Ono Y;Hoshino M.;藤山知之,星野幹雄
• 通讯作者: 藤山知之,星野幹雄

病態生化学研究部 研究業績リスト

病理生化研究室科研成果一览表

A genetic analysis of hypothalamic development and function using Ptf1a-cre & Ptf1a-flox mice

使用 Ptf1a-cre 对下丘脑发育和功能进行遗传分析

• 发表时间: 2012
• 作者: Hori K;Taya S;Nishioka T;Kumanogoh H;Kaibuchi K;Hoshino M;藤山知之,早瀬ヨネ子,長岡麻衣,熊ノ郷晴子,柳川右千夫,マグヌソンマーク,小幡邦彦,田中智宏,伊村明浩,船戸弘正,川口義弥,鍋島陽一,星野幹雄
• 通讯作者: 藤山知之,早瀬ヨネ子,長岡麻衣,熊ノ郷晴子,柳川右千夫,マグヌソンマーク,小幡邦彦,田中智宏,伊村明浩,船戸弘正,川口義弥,鍋島陽一,星野幹雄

Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum.

• DOI: 10.1038/ncomms4337
• 发表时间: 2014
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Seto Y;Nakatani T;Masuyama N;Taya S;Kumai M;Minaki Y;Hamaguchi A;Inoue YU;Inoue T;Miyashita S;Fujiyama T;Yamada M;Chapman H;Campbell K;Magnuson MA;Wright CV;Kawaguchi Y;Ikenaka K;Takebayashi H;Ishiwata S;Ono Y;Hoshino M
• 通讯作者: Hoshino M

A genetic analysis of hypothalamic development and function by using Ptf1a-genetically modified mice

使用 Ptf1a 转基因小鼠对下丘脑发育和功能进行遗传分析

• 发表时间: 2013
• 作者: Fujiyama T;Nagaoka M;Kumanogoh H;Hayase Y;Funato H;Yanagisawa M;Tanaka T;Imura A;Yanagawa Y;Magnuson MA;Wright CV;Obata K;Kawaguchi Y;Nabeshima Y;Hoshino M
• 通讯作者: Hoshino M