Details of a Researcher - Okano, Hideyuki

Papers - Okano, Hideyuki

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Wnt Signaling and a Hox Protein Cooperatively Regulate PSA-3/Meis to Determine Daughter Cell Fate after Asymmetric Cell Division in C. elegans

Arata Yukinobu, Kouike Hiroko, Zhang Yanping, Herman Michael A., Okano Hideyuki, Sawa Hitoshi

Developmental Cell 11 ( 1 ) 105 - 115 2006.07

ISSN 1534-5807

Asymmetric cell division is a mechanism for achieving cellular diversity. In C. elegans, many asymmetric cell divisions are controlled by the Wnt-MAPK pathway through POP-1/TCF. It is poorly understood, however, how POP-1 determines the specific fates of daughter cells. We found that nob-1/Hox, ceh-20/Pbx, and a Meis-related gene, psa-3, are required for asymmetric division of the T hypodermal cell. psa-3 expression was asymmetric between the T cell daughters, and it was regulated by POP-1 through a POP-1 binding site in the psa-3 gene. psa-3 expression was also regulated by NOB-1 and CEH-20 through a NOB-1 binding sequence in a psa-3 intron. PSA-3 can bind CEH-20 and function after the T cell division to promote the proper fate of the daughter cell. These results indicate that cooperation between Wnt signaling and a Hox protein functions to determine the specific fate of a daughter cell. © 2006 Elsevier Inc. All rights reserved.

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Wnt signaling and a Hox protein cooperatively regulate PSA-3/Meis to determine daughter cell fate after asymmetric cell division in C-elegans

Arata, Yukinobu, Kouike, Hiroko, Zhang, Yanping, Herman, Michael A., Okano, Hideyuki, Sawa, Hitoshi

DEVELOPMENTAL CELL 11 ( 1 ) 105 - 115 2006.07

Research paper (scientific journal), ISSN 1534-5807

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Enhanced neurogenesis in the ischemic striatum following EGF-induced expansion of transit-amplifying cells in the subventricular zone

Ninomiya, Mikiko, Yamashita, Toru, Araki, Nobuo, Okano, Hideyuki, Sawamoto, Kazunobu

NEUROSCIENCE LETTERS 403 ( 1-2 ) 63 - 67 2006.07

Research paper (scientific journal), ISSN 0304-3940

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Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury

Okada, Seiji, Nakamura, Masaya, Katoh, Hiroyuki, Miyao, Tamaki, Shimazaki, Takuya, Ishii, Ken, Yamane, Junichi, Yoshimura, Akihiko, Iwamoto, Yukihide, Toyama, Yoshiaki, Okano, Hideyuki

NATURE MEDICINE 12 ( 7 ) 829 - 834 2006.07

Research paper (scientific journal), ISSN 1078-8956

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Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice

Hara Taichi, Nakamura Kenji, Matsui Makoto, Yamamoto Akitsugu, Nakahara Yohko, Suzuki-Migishima Rika, Yokoyama Minesuke, Mishima Kenji, Saito Ichiro, Okano Hideyuki, Mizushima Noboru

Nature 441 ( 7095 ) 885 - 889 2006.06

ISSN 0028-0836

Autophagy is an intracellular bulk degradation process through which a portion of the cytoplasm is delivered to lysosomes to be degraded. Although the primary role of autophagy in many organisms is in adaptation to starvation, autophagy is also thought to be important for normal turnover of cytoplasmic contents, particularly in quiescent cells such as neurons. Autophagy may have a protective role against the development of a number of neurodegenerative diseases. Here we report that loss of autophagy causes neurodegeneration even in the absence of any disease-associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5) specifically in neural cells develop progressive deficits in motor function that are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons. In Atg5^-/- cells, diffuse, abnormal intracellular proteins accumulate, and then form aggregates and inclusions. These results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration. © 2006 Nature Publishing Group.

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Dynamic temporal and cell type-specific expression of Wnt signaling components in the developing midbrain

Rawal Nina, Castelo-Branco Gonçalo, Sousa Kyle M., Kele Julianna, Kobayashi Kazuto, Okano Hideyuki, Arenas Ernest

Experimental Cell Research 312 ( 9 ) 1626 - 1636 2006.05

ISSN 0014-4827

Wnt1 and -5a have been shown to modulate the proliferation and differentiation of midbrain dopaminergic (DA) neurons. However, it is not known whether other Wnts or which Frizzled (Fz) receptors are expressed in the developing midbrain. We found that 13 out of 19 Wnts, all 10 Fzs, and several intracellular Wnt signaling modulators, including Axin, FRAT, Naked, Par-1, and Ltap are developmentally regulated between embryonic days (E) 10.5 and 15.5. Next, we studied whether Fzs are differentially expressed in different cell types and examined neuronal-progenitor- or glial-enriched cultures and DA neurons isolated from TH-GFP reporter mice. We found that Fz8 is expressed at high levels in DA neurons at E11.5 and E13.5. Fz6 and -7 are the predominant transcripts in glial precursors, and Fz9, which is absent in DA neurons at E11.5, is the main receptor expressed in neuronal precursors. We therefore examined the function of Fz9 in DA cells and found that overexpression of Fz9 reduced Wnt5a- but not Wnt3a-induced hyperphosphorylation of Dishevelled. Thus, our results show that Fzs are developmentally regulated and differentially expressed in VM precursors, DA neurons, and glia. These findings suggest that Fz expression contributes to provide specificity to Wnt-mediated effects. © 2006 Elsevier Inc. All rights reserved.

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The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon

Miyagi Satoru, Nishimoto Masazumi, Saito Tetsuichiro, Ninomiya Mikiko, Sawamoto Kazunobu, Okano Hideyuki, Muramatsu Masami, Oguro Hideyuki, Iwama Atsushi, Okuda Akihiko

Journal of Biological Chemistry 281 ( 19 ) 13374 - 13381 2006.05

ISSN 0021-9258

Sox2 is expressed at high levels in neuroepithelial stem cells and persists in neural stem/progenitor cells throughout adulthood. We showed previously that the Sox2 regulatory region 2 (SRR2) drives strong expression in these cells. Here we generated transgenic mouse strains with the β-geo reporter gene under the control of the SRR2 in order to examine the spatiotemporal function of this regulatory region. We show that the SRR2 functions specifically in neural stem/progenitor cells. However, unlike Nestin 2nd intronic enhancer, the SRR2 shows strong regional specificity functioning only in restricted areas of the telencephalon but not in any other portions of the central nervous system such as the spinal cord. We also show by in vitro clonogenic assay that at least some of these SRR2-functioning cells possess the hallmark properties of neural stem cells. In adult brains, we could detect strong β-geo expression in the subventricular zone of the lateral ventricle and along the rostral migrating stream where actively dividing cells reside. Chromatin immunoprecipitation assays reveal interactions of POU and Sox factors with SRR2 in neural stem/progenitor cells. Our data also suggest that the specific recruitment of these proteins to the SRR2 in the telencephalon defines the spatiotemporal activity of the enhancer in the developing nervous system. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

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A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult neural stem cells

Sakaguchi Masanori, Shingo Tetsuro, Shimazaki Takuya, Okano Hirotaka James, Shiwa Mieko, Ishibashi Satoru, Oguro Hideyuki, Ninomiya Mikiko, Kadoya Toshihiko, Horie Hidenori, Shibuya Akira, Mizusawa Hidehiro, Poirier Françoise, Nakauchi Hiromitsu, Sawamoto Kazunobu, Okano Hideyuki

Proceedings of the National Academy of Sciences of the United States of America 103 ( 18 ) 7112 - 7117 2006.05

ISSN 0027-8424

In the subventricular zone of the adult mammalian forebrain, neural stem cells (NSCs) reside and proliferate to generate young neurons. We screened factors that promoted the proliferation of NSCs in vitro by a recently developed proteomics technique, the ProteinChip system. In this screen, we identified a soluble carbohydrate-binding protein, Galectin-1, as a candidate. We show herein that Galectin-1 is expressed in a subset of slowly dividing subventricular zone astrocytes, which includes the NSCs. Based on results from intraventricular infusion experiments and phenotypic analyses of knockout mice, we demonstrate that Galectin-1 is an endogenous factor that promotes the proliferation of NSCs in the adult brain. © 2006 by The National Academy of Sciences of the USA.

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Novel Oncolytic HSV-1 Mutant Expressing ICP 34.5 under the Transcriptional Control of Musashi1 Promoter for the Treatment of Gliomas

Yazaki, Takahito, Kanai, Ryuichi, Okano, Hideyuki, Kawase, Takeshi

MOLECULAR THERAPY 13 S361 - S361 2006.05

Research paper (scientific journal), ISSN 1525-0016

Role of Numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2

Nishimura Takashi, Yamaguchi Tomoya, Tokunaga Akinori, Hara Akitoshi, Hamaguchi Tomonari, Kato Katsuhiro, Iwamatsu Akihiro, Okano Hideyuki, Kaibuchi Kozo

Molecular Biology of the Cell 17 ( 3 ) 1273 - 1285 2006.03

ISSN 1059-1524

Numb has been implicated in cortical neurogenesis during nervous system development, as a result of its asymmetric partitioning and antagonizing Notch signaling. Recent studies have revealed that Numb functions in clathrin-dependent endocytosis by binding to the AP-2 complex. Numb is also expressed in postmitotic neurons and plays a role in axonal growth. However, the functions of Numb in later stages of neuronal development remain unknown. Here, we report that Numb specifically localizes to dendritic spines in cultured hippocampal neurons and is implicated in dendritic spine morphogenesis, partially through the direct interaction with intersectin, a Cdc42 guanine nucleotide exchange factor (GEF). Intersectin functions as a multidomain adaptor for proteins involved in endocytosis and cytoskeletal regulation. Numb enhanced the GEF activity of intersectin toward Cdc42 in vivo. Expression of Numb or intersectin caused the elongation of spine neck, whereas knockdown of Numb and Numb-like decreased the protrusion density and its length. Furthermore, Numb formed a complex with EphB2 receptor-type tyrosine kinase and NMDA-type glutamate receptors. Knockdown of Numb suppressed the ephrin-B1-induced spine development and maturation. These results highlight a role of Numb for dendritic spine development and synaptic functions with intersectin and EphB2. © 2006 by The American Society for Cell Biology.

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Proinflammatory cytokines expression in noise-induced damaged cochlea

Fujioka Masato, Kanzaki Sho, Okano Hirotaka James, Masuda Masatsugu, Ogawa Kaoru, Okano Hideyuki

Journal of Neuroscience Research 83 ( 4 ) 575 - 583 2006.03

ISSN 0360-4012

Recent studies have showed that inflammatory responses occur in inner ear under various damaging conditions including noise-overstimulation. We evaluated the time-dependent expression of proinflammatory cytokines in noise-exposed rat cochlea. Among several detected cytokines, real-time RT-PCR showed that interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were significantly induced 3 hr after noise exposure, and quickly downregulated to the basal level. Tumor necrosis factor-alpha (TNF-α) was also slightly upregulated immediately after noise exposure, Immunohistochemical analysis showed that IL-6 expression was distinctively induced within the lateral side of the spiral ligament. Sequential expression analysis showed that IL-6 immunoreactivity was initially found in the cytoplasm of lateral wall cells, including Type IV and III fibrocytes, and expanded broader throughout the lateral wall, finally to the stria vascularis. Because of the negative Iba-1 staining, IL-6 expression in the early-phase was not due to macrophage or microglia activation. IL-6 was also detected in spiral ganglion neurons at 12 and 24 hr after noise exposure. Our data demonstrates the production of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in early phase of noise overstimulated cochlea. IL-6 expression was observed in the spiral ligament, stria vascularis, and spiral ganglion neurons. These cytokines, produced by the cochlear structure itself in response to noise exposure, may initiate an inflammatory response and have some role in the mechanism of noise-induced cochlear damage. © 2006 Wiley-Liss, Inc.

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Histopathological and behavioral improvement of murine mucopolysaccharidosis type VII by intracerebral transplantation of neural stem cells

Fukuhara Yasuyuki, Li Xiao Kang, Kitazawa Yusuke, Inagaki Masumi, Matsuoka Kentaro, Kosuga Motomichi, Kosaki Rika, Shimazaki Takuya, Endo Hitoshi, Umezawa Akihiro, Okano Hideyuki, Takahashi Takao, Okuyama Torayuki

Molecular Therapy 13 ( 3 ) 548 - 555 2006.03

ISSN 1525-0016

The therapeutic efficacy of neural stem cell transplantation for central nervous system (CNS) lesions in lysosomal storage disorders was explored using a murine model of mucopolysaccharidosis type VII (MPS VII). We used fetal neural stem cells derived from embryonic mouse striata and expanded in vitro by neurosphere formation as the source of graft materials. We transplanted neurospheres into the lateral ventricles of newborn MPS VII mice and found that donor cells migrated far beyond the site of injection within 24 h, and some of them could reach the olfactory bulb. A quantitative measurement indicated that the GUSB activity in the brain was 12.5 to 42.3% and 5.5 to 6.3% of normal activity at 24 h and 3 weeks after transplantation. In addition, histological analysis revealed a widespread decrease in lysosomal storage in the recipient's hippocampus, cortex, and ependyma. A functional assessment with novel-object recognition tests confirmed improvements in behavioral patterns. These results suggest that intracerebral transplantation of neural stem cells is feasible for treatment of CNS lesions associated with lysosomal storage disorders. Copyright © The American Society of Gene Therapy.

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New neurons follow the flow of cerebrospinal fluid in the adult brain

Sawamoto Kazunobu, Wichterle Hynek, Gonzalez-Perez Oscar, Cholfin Jeremy A., Yamada Masayuki, Spassky Nathalie, Murcia Noel S., Garcia-Verdugo Jose Manuel, Marin Oscar, Rubenstein John L R, Tessier-Lavigne Marc, Okano Hideyuki, Alvarez-Buylla Arturo

Science 311 ( 5761 ) 629 - 632 2006.02

ISSN 0036-8075

In the adult brain, neuroblasts born in the subventricular zone migrate from the walls of the lateral ventricles to the olfactory bulb. How do these cells orient over such a long distance and through complex territories? Here we show that neuroblast migration parallels cerebrospinal fluid (CSF) flow. Beating of ependymal cilia is required for normal CSF flow, concentration gradient formation of CSF guidance molecules, and directional migration of neuroblasts. Results suggest that polarized epithelial cells contribute important vectorial information for guidance of young, migrating neurons.

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Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells

Kawada Hiroshi, Takizawa Shunya, Takanashi Tomomi, Morita Yuko, Fujita Jun, Fukuda Keiichi, Takagi Shigeharu, Okano Hideyuki, Ando Kiyoshi, Hotta Tomomitsu

Circulation 113 ( 5 ) 701 - 710 2006.02

ISSN 0009-7322

Background - Hematopoietic cytokines, granulocyte colony-stimulating factor (G-CSF), and stem cell factor (SCF) were reported to show a neuroprotective effect or to support neurogenesis. These cytokines also mobilize bone marrow (BM) cells into the brain, and the BM-derived cells differentiate into neuronal cells. We administered these hematopoietic cytokines after focal cerebral ischemia and assessed their effects and the therapeutic time window for neuronal regeneration. Methods and Results - We induced permanent middle cerebral artery occlusion in mice whose BM had been replaced with BM cells from green fluorescent protein (GFP)-transgenic mice. The occluded mice were treated with G-CSF and SCF in the acute phase (days 1 to 10) or subacute phase (days 11 to 20), and the brain functions and histological changes were evaluated. Separately, we injected bromodeoxyuridine during cytokine treatment to assess cell kinetics in the brain. Six mice were prepared for each experimental group. Administration of G-CSF and SCF in the subacute phase effectively improved not only motor performance but also higher brain function, compared with acute-phase treatment. Acute-phase and subacute-phase treatments identically reduced the infarct volume relative to vehicle treatment. However, subacute-phase treatment significantly induced transition of BM-derived neuronal cells into the peri-infarct area and stimulated proliferation of intrinsic neural stem/progenitor cells in the neuroproliferative zone. Conclusions - Administration of G-CSF and SCF in the subacute phase after focal cerebral ischemia is effective for functional recovery, enhancing cytokine-induced generation of neuronal cells from both BM-derived cells and intrinsic neural stem/progenitor cells. Because G-CSF and SCF are available for clinical use, these findings suggest a new therapeutic strategy for stroke. © 2006 American Heart Association, Inc.

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Distinct functions of human numb isoforms revealed by misexpression in the neural stem cell lineage in the Drosophila larval brain

Toriya Masako, Tokunaga Akinori, Sawamoto Kazunobu, Nakao Keiko, Okano Hideyuki

Developmental Neuroscience 28 ( 1-2 ) 142 - 155 2006.02

ISSN 0378-5866

Mammalian Numb (mNumb) has multiple functions and plays important roles in the regulation of neural development, including maintenance of neural progenitor cells and promotion of neuronal differentiation in the central nervous system (CNS). However, the molecular bases underlying the distinct functions of Numb have not yet been elucidated. mNumb, which has four splicing isoforms, can be divided into two types based on the presence or absence of an amino acid insert in the proline-rich region (PRR) in the C-terminus. It has been proposed that the distinct functions of mNumb may be attributable to these two different types of isoforms. In this study, we used the outer optic anlage (OOA) of the Drosophila larval brain as an assay system to analyze the functions of these two types of isoforms in the neural stem cells, since the proliferation pattern of neuroepithelial (NE) stem cells in the OOA closely resembles that of the vertebrate neural stem/progenitor cells. They divide to expand the progenitor cell pool during early neurogenesis and to produce neural precursors/neurons during late neurogenesis. Clonal analysis in the OOA allows one to discriminate between the NE stem cells, which divide symmetrically to expand the progenitor pool, and the postembryonic neuroblasts (pNBs), which divide asymmetrically to produce neural precursors (ganglion mother cells), each of which divides once to produce two neurons. We found that in the OOA, the human Numb isoform with a long PRR domain (hNumb-PRRL), which is mainly expressed during early neurogenesis in the mouse CNS, promotes proliferation of both NE cells and pNBs without affecting neuronal differentiation, while the other type of hNumb isoform with a short PRR domain (hNumb-PRRS), which is expressed throughout neurogenesis in the mouse embryonic CNS, inhibits proliferation of the stem cells and promotes neuronal differentiation. We also found that hNumb-PRRS, a functional homologue of Drosophila Numb, more strongly decreases the amount of nuclear Notch than hNumb-PRRL, and could antagonize Notch functions probably through endocytic degradation, suggesting that the two distinct types of hNumb isoforms could contribute to different phases of neurogenesis in the mouse embryonic CNS. Copyright © 2006 S. Karger AG.

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Lecithinized superoxide dismutase (PC-SOD) improved spinal cord injury-induced motor dysfunction through suppression of oxidative stress and enhancement of neurotrophic factor production

Takenaga Mitsuko, Ohta Yuki, Tokura Yukie, Hamaguchi Akemi, Nakamura Masaya, Okano Hideyuki, Igarashi Rie

Journal of Controlled Release 110 ( 2 ) 283 - 289 2006.01

ISSN 0168-3659

PC-SOD (lecithinized superoxide dismutase) is a derivative of human Cu, Zn-SOD conjugated with 4 molecules of lecithin, yet having the enzyme activity of scavenging superoxide anion (O₂^-). Intravenous administration of PC-SOD promoted the recovery from spinal cord injury (SCI)-induced motor dysfunction in a dose-dependent manner in rat model, when evaluated by BBB (Basso Beattie Bresnahan) score. Even when given at 24 h after SCI, PC-SOD (1 mg/kg) significantly improved motor dysfunction. Distribution study demonstrated that PC-SOD gradually accumulated to the injured site. Enzyme-linked immunoassay revealed that PC-SOD prevented quantitative loss of neurons, astrocytes, and oligodendrocytes. PC-SOD inhibited SCI-induced oxidative stress, such as the decrease of free sulfhydryl residue, acetylcholine esterase activity, and the increase of lipid peroxidation. PC-SOD increased the production of neuroprotective factors. HIF-1α gene expression increased following SCI, and PC-SOD further increased it. In conclusion, PC-SOD gradually accumulated and retained at the damaged site to scavenge excessive O ₂^-, and suppressed neuronal death through reducing oxidative stress, increasing neuroprotective factor production and HIF-1α gene expression. © 2005 Elsevier B.V. All rights reserved.

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Expression of Musashi-1 in the rat stomach and changes during mucosal injury and restitution

Nagata Hiroshi, Akiba Yasutada, Suzuki Hidekazu, Okano Hideyuki, Hibi Toshifumi

FEBS Letters 580 ( 1 ) 27 - 33 2006.01

ISSN 0014-5793

Musashi-1 is involved in maintenance of neural stem cells. In the rat stomach, we found some cells in the luminal compartment of the mucosa that stained positively for Musashi-1. These cells were distinct from other cells of epithelial lineage, except for parietal cells, and coexpressed HES5. The Musashi-1-positive cells exfoliated after damage, while Musashi-1 expression in neck cells were upregulated, and proliferating cells diminished before reappearing and increasing in number thereafter. We conclude that a subpopulation of parietal cells acts as a source of Musashi-1, which contributes to rapid re-epithelization by restoration of stem cells and regulation of cell differentiation. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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Disease progression of human SOD1 (G93A) transgenic ALS model rats

Matsumoto Arifumi, Okada Yohei, Nakamichi Masanori, Nakamura Masaya, Toyama Yoshiaki, Sobue Gen, Nagai Makiko, Aoki Masashi, Itoyama Yasuto, Okano Hideyuki

Journal of Neuroscience Research 83 ( 1 ) 119 - 133 2006.01

ISSN 0360-4012

The recent development of a rat model of amyotrophic lateral sclerosis (ALS) in which the rats harbor a mutated human SOD1 (G93A) gene has greatly expanded the range of potential experiments, because the rats' large size permits biochemical analyses and therapeutic trials, such as the intrathecal injection of new drugs and stem cell transplantation. The precise nature of this disease model remains unclear. We described three disease phenotypes: the forelimb-, hindlimb-, and general-types. We also established a simple, non-invasive, and objective evaluation system using the body weight, inclined plane test, cage activity, automated motion analysis system (SCANET), and righting reflex. Moreover, we created a novel scale, the Motor score, which can be used with any phenotype and does not require special apparatuses. With these methods, we uniformly and quantitatively assessed the onset, progression, and disease duration, and clearly presented the variable clinical course of this model; disease progression after the onset was more aggressive in the forelimb-type than in the hindlimb-type. More importantly, the disease stages defined by our evaluation system correlated well with the loss of spinal motor neurons. In particular, the onset of muscle weakness coincided with the loss of approximately 50% of spinal motor neurons. This study should provide a valuable tool for future experiments to test potential ALS therapies. © 2005 Wiley-Liss, Inc.

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Expression of RNA-binding protein Musashi in hair follicle development and hair cycle progression

Sugiyama-Nakagiri Yoriko, Akiyama Masashi, Shibata Shinsuke, Okano Hideyuki, Shimizu Hiroshi

American Journal of Pathology 168 ( 1 ) 80 - 92 2006.01

ISSN 0002-9440

Epithelial stem cells reside in the hair follicle (HF) bulge region and possess the ability to differentiate into a variety of cutaneous epithelial cells. The evolutionarily conserved Musashi family of RNA-binding proteins is associated with maintenance and/or asymmetric cell division of neural progenitor cells, and a mammalian Musashi protein is expressed in various epithelial stem/progenitor cells, including gut, stomach, and mammary gland. Thus, we hypothesized that Musashi might be expressed to stem cells and early progenitor cells of HF epithelium. Reverse transcriptase-polymerase chain reaction and immunoblotting identified Musashi-1 (Msl-1) and Musashi-2 (Msi-2) mRNA and protein in cultured mouse keratinocytes, but only Msi-1 was identified in human keratinocytes. In mice, immunohistochemical studies showed that Msi-1 and Msi-2 were expressed in the epidermis and HFs from E14.5 until adulthood. In the early anagen phase, Msi-1 and Msi-2 were expressed in the bulge and secondary germ cells and subsequently in inner root sheath (IRS) cells, especially the middle IRS cells, during the late anagen phase. In human skin, MsM was detected in fetal HF cells but not in adult HFs. These observations suggest that Musashi functions not only in the asymmetric division of early progenitor cells but also in the differentiation of IKS cells during HF development and hair cycle progression. Copyright © American Society for Investigative Pathology.

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The role of autophagy in intracellular quality control

Hara, Taichi, Nakamura, Kenji, Matsui, Makoto, Yamamoto, Akitsugu, Nakahara, Yohko, Suzuki-Migishima, Rika, Yokoyama, Minesuke, Mishima, Kenji, Saito, Ichiro, Okano, Hideyuki, Mizushima, Noboru

AUTOPHAGY 2 ( 4 ) 355 - 355 2006.01

Research paper (scientific journal), ISSN 1554-8627

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