Neuronal expression of ILEI/FAM3C and its reduction in Alzheimer's disease
Lei Liu, Naoki Watanabe, Hiroyasu Akatsu, Masaki Nishimura
Neuroscience 330 236-246 2016年08月 [査読有り]
© 2016 IBRO.Decrease in brain amyloid-β (Aβ) accumulation is a leading strategy for treating Alzheimer's disease (AD). However, the intrinsic mechanism of the regulation of brain Aβ production is largely unknown. Previously, we reported that ILEI (also referred to as FAM3C) binds to the γ-secretase complex and suppresses Aβ production without inhibiting γ-secretase activity. In this study, we examined ILEI expression in mouse brain using immunohistochemistry and subcellular fractionation. Brain ILEI showed widespread expression in neurons and ependymal cells but not in glial and vascular endothelial cells. Neuronal ILEI resided in perinuclear vesicular structures, which were positive for a marker protein of the trans-Golgi network. Although ILEI immunostaining was negative at synaptic terminals, synaptosome fractionation analysis suggested that ILEI was enriched in presynaptic terminals, particularly in the active zone-docked synaptic vesicles. ILEI expression levels in brain peaked during the postnatal period and declined with age. In comparison with age-matched control brains, the number of ILEI-immunoreactive neurons decreased in AD brains, although the subcellular localization was unaltered. Our results suggest that a decline of ILEI expression may cause accumulation of Aβ in the brain and the eventual development of AD.
Hbp1 regulates the timing of neuronal differentiation during cortical development by controlling cell cycle progression.
Watanabe N, Kageyama R, Ohtsuka T
Development (Cambridge, England) 142(13) 2278-2290 2015年07月 [査読有り]
Gene expression profiling of neural stem cells and identification of regulators of neural differentiation during cortical development
Toshiyuki Ohtsuka, Hiromi Shimojo, Mitsuhiro Matsunaga, Naoki Watanabe, Kohei Kometani, Nagahiro Minato, Ryoichiro Kageyama
Stem Cells 29(11) 1817-1828 2011年11月 [査読有り]
During mammalian brain development, neural stem cells transform from neuroepithelial cells to radial glial cells and finally remain as astrocyte-like cells in the postnatal and adult brain. Neuroepithelial cells divide symmetrically and expand the neural stem cell pool; after the onset of neurogenesis, radial glial cells sequentially produce deep layer neurons and then superficial layer neurons by asymmetric, self-renewing divisions during cortical development. Thereafter, gliogenesis supersedes neurogenesis, while a subset of neural stem cells retain their stemness and lurk in the postnatal and adult brain. Thus, neural stem cells undergo alterations in morphology and the capacity to proliferate or give rise to various types of neural cells in a temporally regulated manner. To shed light on the temporal alterations of embryonic neural stem cells, we sorted the green fluorescent protein-positive cells from the dorsolateral telencephalon (neocortical region) of pHes1-d2EGFP transgenic mouse embryos at different developmental stages and performed gene expression profiling. Among dozens of transcription factors differentially expressed by cells in the ventricular zone during the course of development, several of them exhibited the activity to inhibit neuronal differentiation when overexpressed. Furthermore, knockdown of Tcf3 or Klf15 led to accelerated neuronal differentiation of neural stem cells in the developing cortex, and neurospheres originated from Klf15 knockdown cells mostly lacked neurogenic activities and only retained gliogenic activities. These results suggest that Tcf3 and Klf15 play critical roles in the maintenance of neural stem cells at early and late embryonic stages, respectively. © AlphaMed Press.
Aβ産生抑制分子ILEI/FAM3Cの遺伝子転写制御メカニズム
渡邊直希, 川月章弘, 日比野絵美, 野村礼, 西村正樹
第36回日本認知症学会学術集会 2017年11月
孤発性アルツハイマー病のリスク遺伝子TM2D3の機能解析
川月章弘, 渡邊直希, 日比野絵美, 野村礼, 西村正樹
第36回日本認知症学会学術集会 2017年11月
Aβ産生抑制タンパク質ILEIの構造解析に基づく機能メカニズムの検討
日比野絵美, 森田修平, 野村礼, 川月章弘, 渡邊直希, 西村正樹
第36回日本認知症学会学術集会 2017年11月
Aβ産生抑制タンパク質ILEI/FAM3Cの構造と機能の解析
日比野絵美, 森田修平, 杉田昌岳, 渡邊直希, 川月章弘, 野村礼, 西村正樹
2017年度生命科学系学会合同年次大会 2017年12月
神経系及び非神経系細胞におけるILEI/FAM3C遺伝子の転写制御解析
渡邊直希, 庄司航, 川月章弘, 日比野絵美, 野村礼, 西村正樹
2017年度生命科学系学会合同年次大会 2017年12月
Aβ産生抑制タンパク質ILEI/FAM3Cの脳内発現様式と加齢に伴う発現減少
渡邊直希, 劉磊, 赤津裕康, 西村正樹
第35回日本認知症学会学術集会 2016年12月
Brain distribution and subcellular localization of ILEI/FAM3C and its reduction with aging
Naoki Watanabe,Lei Liu,Masaki Nishimura
第39回 日本神経科学大会 2016年07月 日本神経科学学会
Amyloid‐β蓄積を抑制するILEI/FAM3Cのニューロンにおける発現とアルツハイマー病脳における発現低下
渡邊直希, 劉磊, 赤津裕康, 西村正樹
第39回日本分子生物学会年会 2016年12月
大脳皮質形成期においてHbp1は細胞周期の長さを延長することによってニューロン分化のタイミングを制御する
渡邊直希, 影山龍一郎, 大塚俊之
日本生化学会大会(Web) 2015年
大脳皮質形成期においてHbp1は細胞周期進行の制御を介してニューロン分化のタイミングを制御する
渡邊直希, 大塚俊之, 影山龍一郎
日本分子生物学会年会プログラム・要旨集(Web) 2014年
Gene Expression Profiling of Neural Stem Cells and Identification of Regulators of Neural Differentiation during Cortical Development
OHTSUKA Toshiyuki, SHIMOJO Hiromi, MATSUNAGA Mitsuhiro, WATANABE Naoki, KOMETANI Kohei, MINATO Nagahiro, KAGEYAMA Ryoichiro
日本分子生物学会年会プログラム・要旨集(Web) 2011年