{"created":"2023-06-20T13:21:15.575366+00:00","id":1377,"links":{},"metadata":{"_buckets":{"deposit":"29ae2c82-f22c-4e67-b41e-76bb9615fbf8"},"_deposit":{"created_by":1,"id":"1377","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"1377"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00001377","sets":["2:430:27"]},"author_link":["9736","9737","9735"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"高橋, 弘雄"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"タカハシ, ヒロオ"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2003-09-30"}]},"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_12":{"attribute_name":"要旨","attribute_value_mlt":[{"subitem_description":"  Topographic maps with a defined spatial ordering of neuronal connections are a key feature of the brain's organization.  The most widely used model for studies of the formation of topographic maps is the retinotectal projection.  Chick brain factor-1 (CBF-1), a nasal retina-specific winged-helix transcription factor, is known to prescribe the nasal specificity which leads to the formation of the precise retinotectal map especially along the antero-posterior (A-P) axis.  However, the molecular mechanisms by which CBF-1 controls the expression of topographic molecules have not been elucidated.  In the present study, to gain insight into the downstream target genes of CBF-1, he employed electroporation of a retroviral vector carrying the CBF-1 gene into the optic vesicle, and examined effects of the misexpression of CBF-1 on the expression of topographic molecules and other asymmetrically distributed molecules.  The in ovo electroporation of retrovirus allows the immediate and sustained expression of a transgene.  Since endogenous CBF-1 begins to be topographically expressed prior to Hamburger-Hamilton (HH) stage 11 in native embryos, at which stage the polarity along the nasotemporal (N-T) axis appears to be determined, this in ovo electroporation system is suitable for the functional study of CBF-1.  Here, he shows that ectopic expression of CBF-1 in the temporal retina represses expression of EphA3 and CBF-2, and induces that of SOHo-1, GH6, ephrin-A2, and ephrin-A5.  A chimeric protein that consists of an even-skipped repression domain and CBF-1 DNA binding domain exerted the same effects as the wild-type CBF-1 on the expression of S0Ho-1, GH6, EphA3, CBF-2, and ephrin-AS, but not on that of ephrin-A2.  On the other hand, a CBF-1 mutant deficient in DNA-binding activity exerted the same effects as the wild-type CBF-1 on the expression of S0Ho-1, GH6, EphA3, CBF-2, and ephrin-AX, but not ephrin-AS.  These results suggest that CBF-1 controls ephrin-A5 by a DNA binding-dependent mechanism, ephrin-A2 by a DNA binding-independent mechanism, and CBF-2, SOHo-1, GH6, and EphA3 by dual mechanisms.<br />  Our lab recently identified a novel secreted molecule, Ventroptin, which is an antagonist of bone morphogenetic protein 4 (BMP-4) in the retina, and demonstrated that Ventroptin is implicated in the retinotectal topographic projection along both the dorsoventral (D-V) and A-P axes.  Asymmetrical expression of Ventroptin along the N-T axis regulates the graded expression of ephrin-A2 along this axis but not of ephrin-A5 or EphA3 in the retina, which is associated with the retinotectal mapping along the A-P axis.  Vneroptin expression is ventral-specific, complementary to the dorsal-specific BMP-4 expression at the early developmental stage of the retina.  However, along with a decline of BMP-4 expression from the dorsal retina, the expression of Ventroptin forms a double-gradient pattern along the two axes from E6.  This suggests that a member of the TGF-□ family other thin BMP-4 should appear in a temporal high-nasal low gradient along the N-T axis with a complementary pattern to the Ventroptin expression.  In this study, he found that a TGF-□ family member, BMP-2, is expressed in a pattern complementary to that of Ventroptin, with a double-gradient along the two axes from E6 onward.  Ventroptin antagonizes BMP-2 as well as BMP-4.  Misexpression of BMP-2 in the developing retina repressed expression of Ventroptin and ephrin-A2.  Moreover, he demonstrates that CBF-1 perturbs BMP-2 signaling through a DNA binding-independent mechanism, which resultantly causes the induction of ephrin-A2 expression.  These results thus suggest that CBF-1 is located at the top of the gene cascade for the regional specification along the N-T axis in the retina and distinct BMP signals play pivotal roles in the topographic projection along both axes.","subitem_description_type":"Other"}]},"item_1_description_18":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","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725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":"X2 分子生物機構論専攻"}]},"item_1_text_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_text_value":"2003"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"TAKAHASHI, Hiroo","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"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","filename":"甲725_要旨.pdf","filesize":[{"value":"252.5 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"要旨・審査要旨 / Abstract, Screening Result","url":"https://ir.soken.ac.jp/record/1377/files/甲725_要旨.pdf"},"version_id":"e09a4a1e-5437-4210-8965-0477b36c739d"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲725_本文.pdf","filesize":[{"value":"2.1 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"本文","url":"https://ir.soken.ac.jp/record/1377/files/甲725_本文.pdf"},"version_id":"071f26ec-c9da-4c29-bb03-47b86dc9f5fc"}]},"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":"CBF-1 Controls the Retinotectal Topographic Map along the Anteroposterior Axis through Multiple Mechanisms","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"CBF-1 Controls the Retinotectal Topographic Map along the Anteroposterior Axis through Multiple Mechanisms"},{"subitem_title":"CBF-1 Controls the Retinotectal Topographic Map along the Anteroposterior Axis through Multiple Mechanisms","subitem_title_language":"en"}]},"item_type_id":"1","owner":"1","path":["27"],"pubdate":{"attribute_name":"公開日","attribute_value":"2010-02-22"},"publish_date":"2010-02-22","publish_status":"0","recid":"1377","relation_version_is_last":true,"title":["CBF-1 Controls the Retinotectal Topographic Map along the Anteroposterior Axis through Multiple Mechanisms"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T14:44:28.460383+00:00"}