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The Notch-Hes pathway in mammalian neural development

Cell Research 1999年第3期9卷 179-188页

作者： kageyama ryoichiro TOSHIYUKI OHTSUKA(Institute for Virus Research, Kyoto University, Sakyo-ku,Kyoto 606-8507 Japan) 1Institute for Virus Research Kyoto University Sakyo-ku Kyoto 606-8507 Japan 1Institute for Virus Research Kyoto University Sakyo-ku Kyoto 606-8507 Japan

A wide variety of neurons and gIial cells differentiatefrom common precursor cells in the developing nervoussystem. During this process, Notch-mediated cell-cell in-teraction is essential for maintenance of dividing cells andsubsequellt generation of cell type diversity. Activation ofNotch inhibits cellular differentiation, and abnormality ofthe Notch pathway leads to premature neuronal differenti-ation, the lack of some cell types, and severe defects of tis-sue morphogenesis. Recent data demonstrate that Notchfails to inhibit cellular differentiation in the absence of thebHLH genes Hes1 and He5, which functionally afitago-nize the neuronal bHLH genes such as theh1- These re-sults indicate that the two Hes genes are essential effecorsfor the Notch pathway and that neuronal differentiation iscontrolled by the pathway "Notch-+He1/Hs5,Mish1".

关键词： bHLH Hes lateral inhibition neuron Notch

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BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rankl/Opg expression ratio in osteoblasts

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Bone Research 2020年第3期8卷 365-378页

作者： Yuhei Yahiro Shingo Maeda Masato Morikawa Daizo Koinuma Go Jokoji Toshiro ljuin Setsuro Komiya ryoichiro kageyama Kohei Miyazono Noboru Taniguchi Department of Orthopaedic Surgery Kagoshima UniversityKagoshimaKagoshima 890-8520Japan Department of Medical Joint Materials Kagoshima UniversityKagoshimaKagoshima 890-8520Japan Department of Bone and Joint Medicine Kagoshima UniversityKagoshimaKagoshima 890-8520Japan Department of Molecular Pathology Graduate School of MedicineThe University of TokyoBunkyo-kuTokyo 113-0033Japan Institute for Frontier Life and Medical Sciences Kyoto UniversitySakyo-kuKyoto 606-8507Japan

Adult bone structural integrity is maintained by remodeling via the coupling of osteoclastic bone resorption and osteoblastic bone *** or osteoblasts express receptor activator of nuclear factor k-B ligand(Rankl)or osteoprotegerin(Opg)to promote or inhibit osteoclastogenesis,*** morphogenetic protein(BMP)is a potent bone inducer,but its major role in adult bone is to induce osteocytes to upregulate sclerostin(Sost)and increase the Rankl/Opg expression ratio,resulting in promotion of ***,the precise effect of BMP-target gene(s)in osteoblasts on the Rankl/Opg expression ratio remains *** the present study,we identified atonal homolog 8(Atoh8),which is directly upregulated by the BMPSmadl axis in *** vivo,Atoh8 was detected in osteoblasts but not osteocytes in adult *** global Atoh8-knockout mice showed only a mild phenotype in the neonate skeleton,the bone volume was decreased and osteoclasts were increased in the adult ***8-null marrow stroma cells were more potent than wild-type cells in inducing osteoclastogenesis in marrow ***8 loss in osteoblasts increased Runx2 expression and the Rankl/Opg expression ratio,while Runx2 knockdown normalized the Rankl/Opg expression ***,Atoh8 formed a protein complex with Runx2 to inhibit Runx2 transcriptional activity and decrease the Rankl/Opg expression *** results suggest that bone remodeling is regulated elaborately by BMP signaling;while BMP primarily promotes bone resorption,it simultaneously induces Atoh8 to inhibit Runx2 and reduce the Rankl/Opg expression ratio in osteoblasts,suppressing osteoclastogenesis and preventing excessive BMP-mediated bone resorption.

关键词： Runx2 osteoclast BMP

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Id Sustains Hesl Expression to Inhibit Precocious Neurogenesis by Releasing Negative Autoregulation of Hes1

Id Sustains Hesl Expression to Inhibit Precocious Neurogenes...

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中国遗传学会“发育、遗传和疾病”研讨会

作者： Yoshifumi Yokota Robert Benezra ryoichiro kageyama Francois Guillemot Department of Molecular Genetics School of Medicine University of Fukui 23-3 Shimoaizuki Matsuoka Fukui 910-1193 Japan Department of Cancer Biology and Genetics Memorial Sloan-Kettering Cancer Center New York New York 10021 USA Institute for Virus Research Kyoto University Kyoto 606-8507 Japan Division of Molecular Neurobiology National Institute for Medical Research The Ridgeway Mill Hill London NW7

Negative bHLH transcription factor Hesl can inhibit neural stem cells(NSCs)from precocious neurogenesis through repressing proneural gene expression;therefore,sustenance of Hesl expression is crucial for NSC pool ***,we find that lds,the dominant=negative regulators of proneural proteins,are expressed prior to proneural genes and share an overlapping expression pattern with Hesl in the early neural tube of chick *** of ld2 in the chick hindbrain upregulates Hesl expression and inhibits proneural gene expression and neuronal *** contrast,Hesl expression decreases,proneural gene expression expands and neurogenesis occurs precociously in Id1;Id3 double knockout mice and in Id1-3 RNAi-electroporated chick *** studies show that Id proteins interact directly with Hesl and release the negative feedback autoregulation of Hesl without interfering with its ability to affect other target *** results indicate that Id proteins participate in NSC maintenance through sustaining Hesl expression in early embryos.

关键词： neural stem cell maintenance bHLH proneural gene Id Hesl negative feedback autoregulation

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Id Sustains Hesl Expression to Inhibit Precocious Neurogenesis by Releasing Negative Autoregulation of Hes1

Id Sustains Hesl Expression to Inhibit Precocious Neurogenes...

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中国细胞生物学学会第九次会员代表大会暨青年学术大会

作者： Yoshifumi Yokota Robert Benezra ryoichiro kageyama Francois Guillemot Department of Molecular Genetics School of MedicineUniversity of Fukui23-3ShimoaizukiMatsuokaFukui 910-1193Japan Department of Cancer Biology and Genetics Memorial Sloan-Kettering Cancer CenterNew YorkNew York 10021USA Institute for Virus Research Kyoto UniversityKyoto 606-8507Japan Division of Molecular Neurobiology National Institute for Medical ResearchThe RidgewayMill HillLondon NW7 1AAUK

关键词： neural stem cell maintenance bHLH proneural gene Id Hes1 negative feedback autoregulation

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Role of Mash Ⅰ in Lung Growth and Differentiation using Mash Ⅰ Defictent Mice

Role of Mash Ⅰ in Lung Growth and Differentiation using Mas...

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Third Congress of the Asian-Pacific Organization for Cell Biology

作者： Naoko UDAKA Takaaki ITO Takayuki IKOMA Hitoshi KITAMURA ryoichiro kageyama Pathol. Division Kanagawa Cardiovascular Respiratory Center6-16-1 TomiokahigashiKana/awa-kuYokohama Dept of Pathol. Yokohama City Univ Sch of Medicine3-9 FukuuraKanazawa-kuYokohama Institute for Virus Research.kyoto Univ. 53 Shougoin KawaramachiSakyou-kuKyotoJAPAN

In vertebrates,a basic helix-loop-helix transcription factor that is homologous to the Drosophila achaete-scute complex plays a critical role in the development and differentiation in neural cells and neuroendocrine cells. In the lung, pulumonary neuroendoerine cells(PNEC) are distributed throughout the intraplumonary airway Trom the large bronehi to the alveolar duets, which occur

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