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

2013 Fiscal Year Final Research Report

• Project/Area Number: 24800088
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: 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)
• Principal Investigator: FUJIYAMA Tomoyuki 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (00635089)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Keywords: 神経発生 / 視床下部 / マウス / エネルギー消費 / Ptf1a / 神経上皮

Research Abstract

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.

Research Products

• [Journal Article] Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum (2014)
  • Author(s): 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
  • Journal Title: Nature Communications Volume: 5 Pages: 3337
  • DOI: 10.1038/ncomms4337
  • Peer Reviewed
• [Journal Article] Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear (2013)
  • Author(s): Chonko KT, Jahan I, Stone J, Wright MC, Fujiyama T, Hoshino M, Fritzsch B, Maricich SM
  • Journal Title: Developmental Biology (Elsevier Inc.) Volume: 381(2) Pages: 401-410
  • DOI: 10.1016/j.ydbio.2013.06.022
  • Peer Reviewed
• [Presentation] 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 (2013)
  • Author(s): 藤山知之、長岡麻衣、熊ノ郷晴子、早瀬ヨネ子、船戸弘正、川口義弥、鍋島陽一、星野幹雄
  • Organizer: 平成24年度国立精神・神経医療研究センター神経研究所発表会
  • Place of Presentation: 東京
  • Year and Date: 20130321-22
• [Presentation] A genetic analysis of hypothalamic development and function by using Ptf1a-genetically modified mice (2013)
  • Author(s): Fujiyama T, Nagaoka M, Kumanogoh H, Hayase Y, Funato H, Yanagisawa M, Tanaka T, Imura A, Yanagawa Y, Magnuson MA, Wright CVE, Obata K, Nabeshima Y, Hoshino M
  • Organizer: 43^<th> Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego
  • Year and Date: 2013-11-09
• [Presentation] 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 (2013)
  • Author(s): 藤山知之,長岡麻衣,熊ノ郷晴子,早瀬ヨネ子,船戸弘正,田中智洋,伊村明浩,柳川右千夫, Mark Magnuson,小幡邦彦,川口義弥,鍋島陽一,星野幹雄
  • Organizer: 第6回神経発生討論会
  • Place of Presentation: 和光
  • Year and Date: 2013-03-15
• [Presentation] 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 (2012)
  • Author(s): 藤山知之,長岡麻衣,熊ノ郷晴子,船戸弘正,田中智洋,伊村明浩,柳川右千夫, Mark Magnuson,小幡邦彦,川口義弥,鍋島陽一,星野幹雄
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-11
• [Presentation] 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 (2012)
  • Author(s): 藤山知之,早瀬ヨネ子、長岡麻衣,熊ノ郷晴子,柳川右千夫, Mark Magnuson,小幡邦彦,田中智洋、伊村明浩、船戸弘正、川口義弥,鍋島陽一,星野幹雄
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-18
• [Presentation] 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 (2012)
  • Author(s): 藤山知之,早瀬ヨネ子、長岡麻衣,熊ノ郷晴子,柳川右千夫, Mark Magnuson,小幡邦彦,田中智洋、伊村明浩、川口義弥,鍋島陽一,星野幹雄
  • Organizer: 包括脳・夏のワークショップ
  • Place of Presentation: 仙台
  • Year and Date: 2012-07-26
• [Remarks]
  • URL: http://www.ncnp.go.jp/nin/guide/r_diag/Publications.html