{"_buckets": {"deposit": "e0879f9d-3560-4d3e-88dd-e43698ae1bb8"}, "_deposit": {"created_by": 1, "id": "1030", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "1030"}, "status": "published"}, "_oai": {"id": "oai:ir.soken.ac.jp:00001030", "sets": ["20"]}, "author_link": ["0", "0", "0"], "item_1_biblio_info_21": {"attribute_name": "書誌情報（ソート用）", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2007-03-23", "bibliographicIssueDateType": "Issued"}, "bibliographic_titles": [{}]}]}, "item_1_creator_2": {"attribute_name": "著者名", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "伊藤, 圭祐"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_creator_3": {"attribute_name": "フリガナ", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "イトウ, ケイスケ"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_date_granted_11": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2007-03-23"}]}, "item_1_degree_grantor_5": {"attribute_name": "学位授与機関", "attribute_value_mlt": [{"subitem_degreegrantor": [{"subitem_degreegrantor_name": "総合研究大学院大学"}]}]}, "item_1_degree_name_6": {"attribute_name": "学位名", "attribute_value_mlt": [{"subitem_degreename": "博士（理学）"}]}, "item_1_description_1": {"attribute_name": "ID", "attribute_value_mlt": [{"subitem_description": "2007044", "subitem_description_type": "Other"}]}, "item_1_description_12": {"attribute_name": "要旨", "attribute_value_mlt": [{"subitem_description": "The brain functions are accomplished via communications between vast numbers of \u003cbr /\u003eneurons. Thus, the construction of elaborated neural networks is indispensable for \u003cbr /\u003eexerting a normal brain functions. Brain development is categorized into several \u003cbr /\u003esteps such as neurogenesis, neuronal migration, axon projection, synaptogenesis, etc. \u003cbr /\u003eAmong them, neuronal migration is one of the most fundamental processes. If \u003cbr /\u003eneurons do not migrate directionally, the consequences wi11 be a chaotic brain \u003cbr /\u003ebecause numerous subtypes of neurons will be randomly intermixed. Neuronal \u003cbr /\u003emigration helps different neuronal populations to segregate into distinctive \u003cbr /\u003ecompartments, whereas it also contributes to the dispersion of one neurohal \u003cbr /\u003epopulation to occupy a large domain. In this way, distinct neuronal populations are \u003cbr /\u003eappropriately arranged in the brain, which enables the complicated brain functions. \u003cbr /\u003e     Neurons migrate basically in two types of streams, radial and tangential. In the \u003cbr /\u003eradial migration, neurons migrate verdcally to the surface of a brain, whereas in the \u003cbr /\u003etangential migration, neurons migrate parallel to the surface. The radial migration is \u003cbr /\u003ea main migratory mode for constructing the six-layer cerebral cortex, and thus this \u003cbr /\u003emode have been well studied by many Laboratories for several decades. However, it \u003cbr /\u003ehas been only recently revealed that the tangential migration is also a critical \u003cbr /\u003emigratory stream for the brain development. The most famous example of the \u003cbr /\u003etangential migration is provided by GABA interneurons, which migrate from the \u003cbr /\u003eventral telencephalon towards the dorsal neocortex thorough the so-called \"dorsal\u003cbr /\u003etangential migration stream\". However, there is also a stream in the opposite \u003cbr /\u003edirection, \"ventral tangential migration\". Although this migration has been far less \u003cbr /\u003estudied compared with the dorsal tangential migration, there is a good model system \u003cbr /\u003efor analyzing the ventral tangential migration, which is lot cells. \u003cbr /\u003e     Lot cells are a neuronal population recognized by monoclonal antibody (mAb) \u003cbr /\u003elot1. It has been revealed that these neurons are involved in the formation of the \u003cbr /\u003elateral olfactory tract (LOT), the fascicle of olfactory bulb axons extending on the \u003cbr /\u003esurface of the telencephalon. Our group previously reproted that newborn lot cells \u003cbr /\u003emigrate through the ventral tangential pathway. During the early developmental \u003cbr /\u003ephase at E9-10, lot cells differentiate from the ventricular zone of the dorsal \u003cbr /\u003eneocortex region, and migrate on the surface of the neocortex ventrally and \u003cbr /\u003etangentially. After finishing the migration, the cells accumulate at the presumptive \u003cbr /\u003eLOT region and make a cellular array, which guides or allows olfactory bulb axons to \u003cbr /\u003eform the accurate LOT. This migration pattern is quite unique from the viewpoint \u003cbr /\u003ethat the cell migration controls the following axon projection, but molecular \u003cbr /\u003emechanisms of the lot cell migration still remain unknown. \u003cbr /\u003e     Our group previously performed combinational culture of early telencephalic \u003cbr /\u003eexplants, and suggested that the lot cell migration is non-cell autonomously \u003cbr /\u003econtrolled by multiple guidance cues; the neocortex region contains gradually \u003cbr /\u003edistributed guidance cues to orient the migrating cells into the ventral direction, \u003cbr /\u003ewhereas the ventral part of the telencephalon has some mechanisms to exclude lot \u003cbr /\u003ecells, probably mediated by short-range repulsive cues. An axon guidance molecule, \u003cbr /\u003eNetrin-1 has an attractive effect on the migration of lot cells in vitro. However, the \u003cbr /\u003eexpression of netrin-1 is only restricted in the ventral part of the telencephalon, .thus \u003cbr /\u003eNetrin-1 knockout mice exhibit only weak defects in the migration of lot cells. These \u003cbr /\u003eresults suggest that some other guidance molecules probably attract the lot cell \u003cbr /\u003emigration. Also the repulsive cues for lot cells, which should be essential for the final \u003cbr /\u003earrangement of the cells, were virtually unidentified. In order to understand \u003cbr /\u003emolecular mechanisms of the lot cell migration, I took two types of approaches; \u003cbr /\u003ecandidate screening and pharmacological perturbation. \u003cbr /\u003e     First, I screened candidate guidance molecules. cDNAs for various guidance \u003cbr /\u003emolecules were transfected into HEK293T line cells, and the cell aggregates \u003cbr /\u003eexpressing the candidate molecules were made. Subsequently, the effects of candidate \u003cbr /\u003emolecules were investigated by co-culturing these cell aggregates with telencephalic \u003cbr /\u003eslices, after labeling the cells in the ventral tangential migration stream with a \u003cbr /\u003efluorescent dye, DiI. Among many candidate molecules, I found that a repulsive axon \u003cbr /\u003eguidance molecule, SemaphOrin3F had a repulsive effect on the lot cell migration. \u003cbr /\u003eSema3F receptor, Neuropilin-2, was expressed in lot cells, and Sema3F was \u003cbr /\u003e\u003cbr /\u003eexpressed in the region surrounding the presumptive LOT region. The cells in \u003cbr /\u003eNeuropilin-2 knockout mice did not respond to Sema3F in the culture system. I \u003cbr /\u003eexamined the distribution pattern of lot cells in Nrp2 knockout mice and found that \u003cbr /\u003esome lot cells were ectopically distributed in the medial region of the telencephalon. \u003cbr /\u003eThe majority of lot cells, however, normally aligned at the presumptive LOT region \u003cbr /\u003eand they did not cross over the presumptive LOT region ventrally. These results \u003cbr /\u003eindicate that Sema3F functions in confinement of lot cells on the surface of the \u003cbr /\u003eneocortex, but not exclusion of cells from the ventral telencephalon \u003cbr /\u003e     Second, I tested various pharmacological drugs in culture, and found that a \u003cbr /\u003eprotein kinase inhibitor, K252a inhibits the migration of lot cells but does not inhibit \u003cbr /\u003ethe extension of leading processes. This result is interesting because it may provide a \u003cbr /\u003enew insight into the mechanisms of neuronal migration. Neurons usually migrate \u003cbr /\u003elong distances by the locomotion mode in which the leading processes and the cell \u003cbr /\u003ebody migrate in a coordinated manner. However, K252a seemed to convert this \u003cbr /\u003emigration mode into the neurite extension mode such as the axon projection or \u003cbr /\u003edendrite extension. Thus, I hoped that the effect of K252a would give an important \u003cbr /\u003eclue for understanding the switch of the migratory modes, and further analyzed this \u003cbr /\u003einteresting phenomenon in the time-lapse video microscopy to detail the kinetics of \u003cbr /\u003ethe effect. This analysis showed that K252a robustly decreased the migration speed \u003cbr /\u003eof cell bodies but not the extension of leading processes. K252a also converted the \u003cbr /\u003elocomotion mode of the cerebellar granule cells into the neurite extension mode, \u003cbr /\u003esuggesting that the switch of the migratory modes by K252a is rather a general \u003cbr /\u003ephenomenon observable in various neuronal populations. I found one drug, \u003cbr /\u003eroscovitine had a similar effect with K252a. Roscovitine is an inhibitor for cycling \u003cbr /\u003edependent kinases (CDK), and thus I overexpressed a dominant negative form of \u003cbr /\u003eneuronal CDK, CDK5 in migrating neurons. Overexpression of the dominant \u003cbr /\u003enegative CDK5 induced the extension of leading processes and slowdowned the \u003cbr /\u003emigration speed of cell bodies. Therefore, CDK5 activity may be one of the critical \u003cbr /\u003ecomponents for the switching of the migratory modes from the locomotion to the \u003cbr /\u003eneurite extension. \u003cbr /\u003e", "subitem_description_type": "Other"}]}, "item_1_description_7": {"attribute_name": "学位記番号", "attribute_value_mlt": [{"subitem_description": "総研大甲第1059号", "subitem_description_type": "Other"}]}, "item_1_select_14": {"attribute_name": "所蔵", "attribute_value_mlt": [{"subitem_select_item": "有"}]}, "item_1_select_8": {"attribute_name": "研究科", "attribute_value_mlt": [{"subitem_select_item": "生命科学研究科"}]}, "item_1_select_9": {"attribute_name": "専攻", "attribute_value_mlt": [{"subitem_select_item": "18 遺伝学専攻"}]}, "item_1_text_10": {"attribute_name": "学位授与年度", "attribute_value_mlt": [{"subitem_text_value": "2006"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "ITO, Keisuke", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "0", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2016-02-17"}], "displaytype": "simple", "download_preview_message": "", "file_order": 0, "filename": "甲1059_要旨.pdf", "filesize": [{"value": "369.0 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_11", "mimetype": "application/pdf", "size": 369000.0, "url": {"label": "要旨・審査要旨", "url": "https://ir.soken.ac.jp/record/1030/files/甲1059_要旨.pdf"}, "version_id": "20cfb715-1163-4f9d-8662-806270411076"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "thesis", "resourceuri": "http://purl.org/coar/resource_type/c_46ec"}]}, "item_title": "Molecular mechanisms of ventral tangential migration of lot cells, the guide post neurons in the lateral olfactory tract", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Molecular mechanisms of ventral tangential migration of lot cells, the guide post neurons in the lateral olfactory tract"}, {"subitem_title": "Molecular mechanisms of ventral tangential migration of lot cells, the guide post neurons in the lateral olfactory tract", "subitem_title_language": "en"}]}, "item_type_id": "1", "owner": "1", "path": ["20"], "permalink_uri": "https://ir.soken.ac.jp/records/1030", "pubdate": {"attribute_name": "公開日", "attribute_value": "2010-02-22"}, "publish_date": "2010-02-22", "publish_status": "0", "recid": "1030", "relation": {}, "relation_version_is_last": true, "title": ["Molecular mechanisms of ventral tangential migration of lot cells, the guide post neurons in the lateral olfactory tract"], "weko_shared_id": 1}