F̂̍\`q̔Ƃ̔j]ɋN锭ُ̈킨ю

<strong> F</strong>
iLww@w ȊwUwj
emailF<a href="mailto:amuto@hiroshima-u.ac.jp">F</a>
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̈Zr[, <strong>4</strong>, e002 (2015)@<a href="http://dx.doi.org/10.7875/leading.author.4.e002">DOI: 10.7875/leading.author.4.e002</a>
Akihiko Muto: <strong>Gene regulation mediated by higher-order chromosome structure and its implications for the pathogenesis of human diseases.</strong>

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<h2>v </h2>
@`q̓K؂Ȑ͍זẺ^@\ɂďdvłC̔j]ُ͔̈⎾Ȃǂ̌ɂȂDgDȂǓ̏󋵂̂Ƃň`q𐧌䂷ٓIȃGnT[́C̑WIƂȂv[^[痣ĂC̃GnT[ƃv[^[Ƃ̒̑ݍpɂ͐F̂̍\̃_Ci~bNȕωKvłDŋ߂̌CRq[V₻̋@\^pNłNIPBLF̂ɂă[v\̌`шێɊ֗^邱ƂCF̂̍\`q̐@\̎ԂXɖ炩ɂĂD̃r[ł́CRq[VNIPBLɂF̂̍\ш`q̐@\Ɋւŋ߂̒mCсC̋@\̌ɂƂȂُ̈⎾̕q@\ɂāCɎl̔ւ̉e𒆐SɁCM҂ɂŋ߂̐ʂ܂D

<h2>͂߂</h2>
@`q̔Ƃ͋`ɂ͓]ʐC`q̋@\K؂ɔ邽߂ɏdvȒiKłD邢͑gDɓٓIȈ`q̔͂܂܂ȍזEɌƒ炵CזEƂĂ̐̋@\ێ邽߂ɕK{łD]ʐ̕q@\P΁Cv[^[ɂGnT[ƌ]ʈqɂRNA|[[̊CƂƂłDlIقǂ܂ɂ́C֘A]ʈq̗̔LёgCgDɉ`q邨ȁiB́jiłDCGsWFleBNXɂ鐧̔F̂̍\ɑ΂闝̐[܂ɂC̍l͈ςDGsWFleBbNƂ΂qXgDNȀC̓N}`̍\ωC]ʐɂ^pŇ⊈̏ԂɉeyڂD]ʂɂ^pNƂẮCÓTIȊ{]ʈqGnT[ȂǂɌ]ʈqɂ킦CqXgCyfN}`fO^pNC]ʐLqȂǁC܂܂ȓ]ʋq݂ĂD܂CR[hRNÂ͂炫dvł邱ƂĂD܂܂Ȑ@\̂ȂŁCM҂͌݁CF̂̍\̖ɋĂD
@F̂͂ĐÓIȂ̂ł͂ȂC̍\̓_Ci~bNɕωD̍ł͕̂̐F̂̋Ïkł낤DCԊ̊jɂĂF̂̓_ɕzĂ킯ł͂ȂC󋵂ɉēK؂Ȕzu邢͍\Ƃ悤䂳ĂDԊɂF̂̓Ԃ𒼐ړIɉ邱Ƃ݂͌ł܂ނDCߔN̐wI邢͕qwIȉ͋Zp̐iɂC̍\𐄑ɑ邾̑̏񂪒񋟂悤ɂȂĂDF̂̍\̉͂́CĂ͌u<em>in situ</em>nCu_C[[Vɂ́íj`qWIƂ͂嗬łCF̍\ߊlichromosome conformation captureF3Cj@̓oƂ̉p@̎ɂQmCh𑜓xȉ͂\ɂȂĎʁCF̂͒IȒPȂgЂhł͂ȂC̒̑ݍpG\̂ł邱Ƃ炩ɂȂĂD܂CN}`Ɖu~ichromatin immunoprecipitationFChIPj@̔WɂCF̂̍\̌`Ɋ֗^^pN̎Ԃ𖾂ĂD̂悤ȉ͂Ə]̈`wI邢͔wIȋ@\͂Ƃ̑gɂCF̂̍\̐̐IȈӋ`炩ɂD

<h2>1DԊ̊jɂF̂̍\</h2>
@F̂̍\͊KwIɐ䂳Ăi<a href="#F1">}1</a>jDꂼ̐F̂͊{IɊjɂēƗԂɃRpNgɎ߂ĂCאڂF̂Ƃ͗̈LȂDF̃eg[Ƃ<a href="#R1"><sup>1)</sup></a>DF̃eg[̓̐F̂͋@\IɓƗMbTCŸ̗ɋ敪ĂCg|WJhCƖÂĂ<a href="#R2"><sup>2)</sup></a>Dg|WJhĈ̋Ëɂ́CCX[^[^pNłCCCTCqtRNA`qCnEXL[sO`qȂǁCCX[^[iEjƂĂ̋@\qxɋǍ݂ĂCאڂg|WJhĈ̕Iȑݍp}@\IȓƗێĂDCF̍\ߊl@̉p@p͂Cg|WJhC̓ɂ͂菬K͂ȑݍp葽̃[v\݂邱Ƃ炩ɂȂ<a href="#R2"><sup>2)</sup></a>Dg|WJhC͐זEȂǂĈłCF̂̍\ՂɂȂĂƍlĂDɑ΂C[v\ɂ͍זEɂِȂǂ̉YF߂邱ƁC܂C̑Ƃăv[^[GnT[Ȃǂ܂ޗ̈悪pxɎgĂ邱ƂȂǂC[v\邢͑gDɓٓIȈ`q̔ɏdvł邱ƂꂽDŋ߂̌ł́C[v\̌`Ƃ`q̔ɃRq[V₻̊֘A^pN̊֗^邱Ƃ炩ɂȂĂ<a href="#R3"><sup>3,4)</sup></a>D

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@Ԋ̊jɂF̂̍\</strong>
iajԊ̊j̓ł́Cꂼ̐F݂̂͌ɍ肠킸CF̃eg[Ƃ΂ŗL̗̈Ɏ܂ĂD
ibjF̂̓CX[^[zȂǂɕx񂾋ËɂMbTCŸ̗Ɏd؂ĂC̓g|WJhCƂ΂DF̗̂̈̂̑ݍp̓g|WJhC̓ɐĂD
icjg|WJhC̓ɂ͑̃[v\݂D̑̓GnT[v[^[̑ݍpɂ`ĂC`qɏdvȍ\ƍlĂD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2015/01/Muto-4.e002-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2015/01/Muto-4.e002-Fig.1.png&amp;caption=fig1-caption-text]


<h2>2DRq[VƎ</h2>
@Rq[V4̃TujbgCSMC1CSMC3CRAD21CSA1/SA2Ȃ郊Õ^pN̂łi<a href="#F2">}2</a>jDזÊƂɎoF̂O̓ɑ˂@\ƍlĂCꂽF̂זEɋϓɕz悤䂵ĂDRq[V̐F̂ւ̌̓Rq[V[_[Ƃ΂CNIPBL/Scc2MAU2/Scc4Ƃ̃^pN̂ɂ萧䂳Ăi<a href="#F2">}2</a>jD̂ōxɕۑĂCזEɂĕK{̂͂炫ĂDRq[V̋@\̌ɂזEBُ̈킪̔ǂɊ֗^Ƃ̎wEC̂זEɂăRq[ṼTujbgR[h`q<em>NIPBL</em>`qɕψق┭ʂ̕ω݂Ă<a href="#R5"><sup>5)</sup></a>DRq[V̋@\sSɂƂȂF̂̕s萫łƂ邪<a href="#R6"><sup>6)</sup></a>CFِ̂̈ƂȂȂP[X݂Ă<a href="#R5"><sup>5)</sup></a>C̗v͖炩ł͂ȂD

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@Rq[VуRq[V[_[</strong>
Rq[V4̃TujbgȂ郊O̍\DꂽoF̂O̓ɑ˂邱ƂɂC̐ڒ𕪗܂ňێƍlĂDRq[VDNAƂ̌ɂ̓Rq[V[_[Ƃ΂NIPBL-MAU2̂̋@\KvłD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2015/01/Muto-4.e002-Fig.2.jpg" target="_blank">[Download]</a></div>[hs_figure id=2&amp;image=/wordpress/wp-content/uploads/2015/01/Muto-4.e002-Fig.2.png&amp;caption=fig2-caption-text]

@<em>NIPBL</em>`qRq[VTujbg̈`q͈`q̔ɂ֗^ĂCꂪ̉ߒɂďdvł邱Ƃ炩ɂȂĂĂDVEWEoG<em>Nipped</em>ψّ̂<em>cut</em>`q̔̒ቺɂ̌`ԈُЂNČ`qƂē肳ꂽ<em>Nipped-B</em>`q<em>NIPBL</em>`q̃VEWEoGɂzOł<a href="#R7"><sup>7)</sup></a>D]ʐ̋@\͐ҒœɂĂۑĂCNIPBLRq[VTujbg̋@\̌ɂЂNCRq[VaƂ΂邢̐Vł͂̈`q̔Ɉُ킪F߂Ă<a href="#R8"><sup>8)</sup></a>D\IȃRq[VałCornelia de LangeǌQ́C<em>NIPBL</em>`q̃nvsSψفiꕔ̌yǂ̊҂ł́CRq[VTujbgRq[V^pNR[h`q̕ψفjɋN鎾ŁCV1lɖ1l̊ŔǂƂĂDSC튯ClȂǂ܂܂Ȋ튯ɂ`ԓI邢͋@\IȈُCjQC_x؂ȂǑɂ킽Ǐ悷<a href="#R9"><sup>9,10)</sup></a>D҂ɗRזEł͂܂܂Ȉ`q̔ʂωĂ邪CoF̂̐ڒɂ͌Ȉُ킪F߂ȂDľʂ́CM҂炪쐻CCornelia de LangeǌQ̃fł<em>Nipbl</em>`qweψك}EXCсCNipbl̔A`ZXtHmISkNI`h̓ɂmbN_E[utBbVɂĂČCCornelia de LangeǌQɂĂ݂邳܂܂Ȉ`q̔̕ω⑽lȕ\^CׂNIPBL̕Iȋ@\̌ɂ萶邱Ƃؖꂽ<a href="#R11"><sup>11-13)</sup></a>Dł́CNIPBL邢̓Rq[V͂ǂ̂悤ɂĈ`q𐧌䂵Ă̂낤H

<h2>3DNIPBL邢̓Rq[Vɂ`q̐@\</h2>
@NIPBLRq[Vɂ`q̐@\ɂĂ͏C܂͂ƂĂȂD܂ł̂܂܂ȒḿC̈قȂ镪q@\݂̑ĂD
@Ƃ͂߂ɒ񏥂ꂽ̂́CF̂̍\@\łDɏqׂCVEWEoG̔ɏdv<em>cut</em>`q̔́C̖85 kb㗬ɂɓٓIȃGnT[ɂ萧䂳ĂCNipped-B͂̃GnT[ƃv[^[Ƃ̒̑ݍpɂďdvł邱Ƃꂽ<a href="#R7"><sup>7)</sup></a>DM̍זEɂẮCOr<a href="#R14"><sup>14)</sup></a> vgJhw<a href="#R15"><sup>15)</sup></a> Ȃǂ̈`q̔₻̈`q̎ӂ̍\̌`ɃRq[Vɑ΂ˑ̂邱Ƃ񍐂ĂD
@NIPBLRq[V̐F̂̍\̐ւ̊֗^́CCX[^[^pNłCCCTCq]ʋqł郁fBG[^[̂ȂǂƂ̋IȍpɂĂxĂDN}`Ɖu~@ɂQmChȉ͂ɂCNIPBLуRq[VƂF̂Ƀ_ɌĂ킯ł͂ȂCɓ]ʂ`q̓]ʊJn_̋ߖTȂǁC̗̈ɔZkXF߂ꂽDRq[V̌p^[CCCTCq̃QmɂǍ݂ƗގĂCwIȉ͂̌ʂƂ킹āCRq[VCCCTCqƂF̂ɂčpxɋǍ݂ݍpĂ邱Ƃꂽ<a href="#R16"><sup>16,17)</sup></a>D̑ݍp͋@\IłCRq[Viɂ郋[v\̌`jCX[^[̎ԂSƁCRq[VCCCTCqƂ̑ݍpƂăCX[^[𔭊ׂK؂ȏꏊɔzu邱ƁCȂǂ炩ɂꂽi<a href="#F3">}3a</a>jD܂ESזEp͂ɂCfBG[^[̂Rq[VCNIPBLCRNA|[[IIȂǂƃv[^[GnT[ɂċǍ݂C[v\̌`ESזË̖ێɂ`q̔𐧌䂵Ă邱Ƃ񍐂ꂽ<a href="#R18"><sup>18)</sup></a>i<a href="#F3">}3b</a>jD̂ɏqׂ悤ɁCfBG[^[̂Ƃ̑ݍṕCESזÊ݂Ȃ炸C̂̔̉ߒɂgDɓٓIȈ`q̔ɂĂdvȖ͂Ăƍl<a href="#R13"><sup>13)</sup></a>D

<a name="F3"></a><div id="fig3-caption-text" style="display: none;"><strong>}3@NIPBLуRq[Vɂ`q̔</strong>
iajRq[VCCCTCqƂƂɃCX[^[@\𔭊D[v\̓ɂ`q́C̓ɂ鐧̈̉eɂ]ʂ䂳DCאڂ̈悩̉e͐C]ʐِ̓ێD
ibjNIPBLCRq[VCfBG[^[̂́CGnT[ƃv[^[Ƃ̒̑ݍp̌`xC]ʂ̊Ɋ^D
icjɊ֗^`qɂ́C]ʊJn̒RNA|[[II̐L}iꎞ~j̋N݂̂Ă邪CɂDSIFNELFȂǂ̓]ʌq֗^ĂD`qhɂ]ʌqRNA|[[IIC[hCiCTDj_C]ʂ̊ԂւƐڂDVEWEoGɂẮC̐L~̉ɂRq[V̊֗^ĂD
idjyɂẮCRq[V[_[Scc2-Scc4̂SWI/SNFN}`fÔƂƂɃkNI\[̂Ȃ̈̌`𑣐iC]ʐɊ֗^邱ƂĂD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2015/01/Muto-4.e002-Fig.3.jpg" target="_blank">[Download]</a></div>[hs_figure id=3&amp;image=/wordpress/wp-content/uploads/2015/01/Muto-4.e002-Fig.3.png&amp;caption=fig3-caption-text]

@F̂ɂ鋤Ǎ݂⑊ݍp炩ɂC̃^pN̖͕KdĂȂƂĂDRq[V̋Ǎ݂CCCTCq̋Ǎ݂̓Qm̍L̈ɂďdĂ邪C`qF̗̂̈̂̑ݍpɂ͂炫ɂ͈ႢF߂D̋@\̓g|WJhČ`ɂĂƂɌŁCǂg|WJhC̋EɌɂ炸CĚ`ɂCCCTCq݂̂֗^Ă<a href="#R19"><sup>19)</sup></a>D܂CRq[VCfBG[^[CNIPBL̋Ǎ݂̗̈悪CRq[VCCCTCq̋Ǎ݂̗̈Ƃ͑傫قȂĂ邱<a href="#R18"><sup>18)</sup></a>CNIPBLRq[VɔˑIɐF̂Ƃ̌`q̔sƂȂǂ񍐂Ă<a href="#R20"><sup>20)</sup></a>Ďʂ́CNIPBLRq[V܂ޕ́i@\IɁjقȂ]ʐ䕡݂̂C炪󋵂ɉĎgĂ\DNIPBL̕ψقɂaԂƃRq[V̕ψقɂaԂKvȂƂƂ֌ŴȂD
@ɍŋ߂ł́CVȓ]ʐ@\ւ̊֗^炩ɂȂĂDVEWEoGp͂ł́CRq[V`q̑RNA|[[IIɂ]ʐL̈ꎞ~F߂ĂC̈ꎞ~̉ɂ̓Rq[VKvł<a href="#R21"><sup>21)</sup></a>i<a href="#F3">}3c</a>jD܂CyłSWI-SNFN}`fÔɂC]ʐɂ̈ɍpxɔF߂kNI\[̂Ȃ̈̌``q̔ɁCScc2-Scc4Rq[V[_[Ƃ̑ݍpKvł邱Ƃꂽ<a href="#R22"><sup>22)</sup></a>i<a href="#F3">}3d</a>jDRNA|[[IÏꎞ~SWI-SNF̂ɂN}`̃fO͐̂ōLp]ʐ@\ł邪CNipblRq[V̊֗^ҒœɂĂۑĂ邩ǂ͍̌҂ȂĂ͂ȂȂD

<h2>4Dl̔̉ߒƈ`q̔</h2>
@|{זEpwI邢͕qwIȉ͂́CNIPBLRq[Vɂ`q̔̕q@\ɂđȒm炵DCCornelia de LangeǌQɂ݂悤Ɍ̃xւ̉e͑lłCۂُ̔̈ɂĂǂ̂悤Ȉ`q֗^Ă̂C܂C̐ɂĂǂ̂悤ȃ^pNƑݍp̂CȂǂɂĂ͑̓_炩ɂĂȂDCM҂́CNIPBL̃mbN_Eɂ̃xł̕\^ƁCŉe`qƂ̈ʊ֌WɒڂCf̌̂p͂Ă<a href="#R11"><sup>11-13)</sup></a>D̒mgݍ킹邱ƂɂCNIPBLуRq[Vɂ锭̐@\̎Ԃqxɂď炩ɂĂĂDȉCŋ߁CM҂炪Ăl̔ƂĉD
@Ғœ̎l͔̔wiw̕ɂČÂ猤ĂC̕q@\ɊւĂ͖cȒm~ςĂD܂Cނїނ͍Đ\ƂCŋ߂ł́CĐ̗̌LpȃfɂȂȂǂӂыrтĂD̎lłMނⒹނ̎ijёirjƋނ̑ΕhiE1΂̃qŁCrƕrjƂ́C`ԓIɂ͑傫قȂ邪iIɂ͋ʂ̋ND̂Ƃ́Cqx̉͂ɂĖmɎCƂɁC̏ɂ鎈ilq̌ǰ`̉ߒ́C̐@\܂ߔɂ悭Ă<a href="#R23"><sup>23)</sup></a>Dlُ̈Cornelia de LangeǌQ̂ƂȏǏ̂ЂƂłC҂̑͐܂ȂɘrCCwȂǎlɂȂ炩̌DǏ̒x͊҂ɂ肳܂܂ł邪CƂNIPBLɕψق҂̈ꕔł͘r̉ʕ傫悤ȏdĂȏǏF߂Dlُ̈́CM҂炪Cornelia de LangeǌQ̃fƂč쐻NipblmbN_E[utBbVɂĂF߂Ă<a href="#R13"><sup>13)</sup></a>Cĕۑꂽl̔̐@\NIPBLdvȖ͂Ă邱ƂD
@͑tɗRԗtn̑gDƂOt̏炩Ȃ튯ŁC̊̃`mC_VOiɂ蕪UDl`̏̒iKł͊ԗtnזȆBɂOɂނĐL邪C̑B͊OtƂ΂[̏gDFgfVOiɈˑĂi<a href="#F4">}4a</a>jDCOtɂ<em>fgf</em>`q̔͊ԗtnזESHHVOiFGF10VOiɂUĂ邪C̈`qC̔ǂHOXDTBX5Ȃǂ̓]ʈq̔ɂ͏dvłi<a href="#F4">}4b</a>jD

<a name="F4"></a><div id="fig4-caption-text" style="display: none;"><strong>}4@[utBbVɂ鎈̔̐</strong>
iaj[utBbV̋r̎DOt炩FgfVOiɂԗtnזȆBiꎈ肪D󐸌42ԂɂāC݂ƂD
ibj[utBbVɂĎ̔ɂ`qJXP[hD̐ߌ`ɂđȎ̐߂̃`mC_VOiɂ莈̕UDMƓlɁCԗtnזEFgf10VOiShhVOiɂOtɂ<em>fgf</em>`q̔UDNipbl⃁fBG[^[̂́C5f-<em>hoxd</em>`q̔Ď̔Ɋ֘A邳܂܂Ȉ`q̔𐧌䂵ĂƗ\zDNipbl邢̓fBG[^[̂̃TujbgłMed12mbN_Eɂĉe`qԐFŎD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2015/01/Muto-4.e002-Fig.4.jpg" target="_blank">[Download]</a></div>[hs_figure id=4&amp;image=/wordpress/wp-content/uploads/2015/01/Muto-4.e002-Fig.4.png&amp;caption=fig4-caption-text]

@<em>HoxD</em>`qQ<em>Shh</em>`q͎̂ق܂܂ȕʂɂĂĂ邪CɓٓIȔ͂̈`q痣ꂽ̈ɂGnT[ɂ萧䂳Ă邱ƂmĂD<em>Hox</em>`qQ͐F̂ɂăNX^[`Ăi<a href="#F5">}5a</a>jCׂĂ̈`q͓̕ɓ]ʂ<a href="#R24"><sup>24)</sup></a>DNX^[̏㗬Ɉʒu`q5f-<em>hox</em>`qCɈʒu`q3f-<em>hox</em>`qƂсC5fɋ߂`qقǑ傫ȔԍĂiƂ΁C}EX<em>HoxD</em>NX^[ł́CƂ㗬i5fj<em>Hoxd13</em>`qCƂi3fj<em>Hoxd1</em>`qʒujDʂ̑c`qQm̔{ɂ蕡̈`qNX^[`ꂽƍlĂ<a href="#R25"><sup>25)</sup></a>CMł<em>HoxA</em>`<em>HoxD</em>4ށC[utBbVȂǂ̍dނł7ށi[utBbVł́C<em>HoxD</em>1CȊOׂ2gj̈`qNX^[݂DNX^[ׂ̂Ă̈`q̓GnT[̋LɂAgāiƗIɁj䂳ĂC`q̑ΓIȈʒuƔ̎ԓIыԓIȃp^[Ƃ̂ɂ݂鑊֐O㎲l̃p^[`ɏdvłD<em>Hox</em>`qQ̎ɓٓIȔ́C`qNX^[ɗאڂ`q̖x̒Ⴂ̈ɑ݂GnT[Ƃ̃[v\̑ݍpɂ萧䂳ĂDɑ΂C̊i_on̑gDjɂ锭Ɋ֗^GnT[́C`qNX^[̓̈`q̋ߖTɋǍ݂邱ƂmĂi<a href="#F5">}5b</a>jD<em>Hox</em>`qQ̑gD̓ٓIȔ̐@\̏ڍׂɂĂ͑̑̂ŁCQƂꂽ<a href="#R24"><sup>24,26)</sup></a>D

<a name="F5"></a><div id="fig5-caption-text" style="display: none;"><strong>}5@NIPBLуfBG[^[̂ɂ<em>hox</em>`qQ̔</strong>
iajNipbl邢̓fBG[^[̂̃TujbgłMed12mbN_E̎ɂ<em>hox</em>`qQ̔̕ωD5f-<em>hox</em>`qׂ̔͂Ēቺ̂ɑ΂C3f-<em>hox</em>`qׂ̔͂ď㏸DDF͖͂̈`q܂͔̂Ȃ`qD
ibjNIPBLуfBG[^[̂ɂ<em>hox</em>`qɂ郋[v\̌`̑iD̊̔ɓٓIȃGnT[̓NX^[̓ɂ̂ɑ΂CɓٓIȃGnT[̓NX^[̊Ö`q̖x̒Ⴂ̈ɑ݂C[v\<em>hox</em>`qQƒ̑ݍpDNIPBL⃁fBG[^[̂̓[v\̌`ĎɓٓI<em>hox</em>`qQ̔Ɋ^ƍlD̑ݍpKvƂȂƍl̊ɂ<em>hox</em>`qQ̔́CNipbl邢̓fBG[^[̂̃TujbgłMed12mbN_EɂĂ͉eȂD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2015/01/Muto-4.e002-Fig.5.jpg" target="_blank">[Download]</a></div>[hs_figure id=5&amp;image=/wordpress/wp-content/uploads/2015/01/Muto-4.e002-Fig.5.png&amp;caption=fig5-caption-text]

@C<em>Shh</em>`q̎ɂ锭ɂĂF̂̍\֗^ĂD<em>Shh</em>`q̎ɓٓIȃGnT[͗אڂ<em>Lmbr1</em>`q̃Cgɑ݂邪CMނ̏ꍇC͖̋1 MbłD}EX̎̍זEp3̌u<em>in situ</em>nCu_C[[Vɂ͂ɂCGnT[ƃv[^[[v\ĕIɑݍpĂ邱ƂĂ<a href="#R27"><sup>27)</sup></a>D

<h2>5D[utBbVfƂl̔ߒɂNipbl̋@\̉</h2>
@ľCornelia de LangeǌQɂ\IȏǏ̂ЂƂł邪C̔ǋ@\̏ڍׂ͖炩łȂDM҂́C[utBbVfƂNipblɂl̔̐@\̉𖾂݂<a href="#R13"><sup>13)</sup></a>D[utBbVɂĂ͑Oirj̔̉ߒqxŏڍׂɉ͂Ă<a href="#R28"><sup>28)</sup></a>C܂C̐@\MƂ̋ʐƂCNipblɂľ`@\̉͂ɔɗLpłD
@[utBbVł́C͎̐󐸌30Ԃ납ώ@C󐸌72Ԃɂ݂͂ڂɂ炩ȃq̌`ԂƂ悤ɂȂDق̐ҒœƓlɁC̐͊ԗtnזȆBƂȂC̐ɂ͊Ot炩FgfVOiKvłDOtɂ<em>fgf</em>`q̔ɕKv<em>shh</em>`q<em>fgf10</em>`q̔́CقȂ`qJXP[h̉ɂĐ䂳ĂC<em>shh</em>`q̐ɂ<em>hand2</em>`q<em>hoxd</em>`qC<em>fgf10</em>`q̐ɂ<em>tbx5</em>`q<em>fgf24</em>`q֗^DNipblmbN_EɂĂ͎̐ɂ邵xF߂CԗtnזȆB̒ቺƂɂƂȂזĚώ@ꂽD̏ƂɁCɏqׂ̔Ɋ֘A`q̔ɂĉ͂ƂCԗtnזEɂHoxd-Hand2-ShhoḦ`q̔CсCOtɂ<em>fgf</em>`q̔ɒቺĂi<a href="#F4">}4b</a>jD<em>HoxD</em>`qQ<em>Shh</em>`q̎ɂ锭<em>Nipbl</em>ψك}EXłቺĂ<a href="#R13"><sup>13)</sup></a>C܂C<em>HoxD</em>`qQ<em>Shh</em>`q̕ψك}EXłCornelia de LangeǌQ̂悤Ȏl̒ZkF߂ꂽƂ<a href="#R29"><sup>29-31)</sup></a>C<em>Hoxd</em>`qQC<em>Hand2</em>`qC<em>Shh</em>`qȂǂCornelia de LangeǌQɂ鎈̌ɂdvȐ_ł\ꂽD
@NipblmbN_E̎ɂĂ<em>hoxd</em>`qQ̔ɓIȉeĂ<a href="#R13"><sup>13)</sup></a>i<a href="#F5">}5a</a>jD[utBbV<em>hoxd</em>NX^[Ɋ܂܂7̈`qׂ͂Nipbl̐䉺ɂDNipbl̃mbN_Eɂe̓NX^[ɂ`q̑ΈʒuƊ֘AĂC̔ɏdv5f-<em>hoxd</em>`qi<em>hoxd9</em>`q`<em>hoxd13</em>`qjׂ̔ĒቺĂ̂ɑ΂CɈʒu3f-<em>hoxd</em>`qi<em>hoxd3</em>`q<em>hoxd4</em>`qjł͔̌ȏ㏸F߂ꂽD܂CNipbl̃mbN_Ẻe͎ɓٓIłC`qNX^[̓̃GnT[ɂ萧䂳̊ɂ锭ɂ͉eyڂȂDɁC3̌u<em>in situ</em>nCu_C[[Vɂ͂ɂC<em>hoxd</em>NX^[̎ӂ̍\NipblɈˑĂ邱Ƃ蒼ړIɏؖ邱Ƃɂ<a href="#R13"><sup>13)</sup></a>Dȏׂ̂Ă̌ʂ́CNipblGnT[ƃv[^[Ƃ̂̑ݍpĈ`q𐧌䂷Ƃƈvi<a href="#F5">}5b</a>jD[ƂɁC<em>hoxd</em>NX^[ɂĂ݂ꂽ5f-<em>hox</em>`q̔}3f-<em>hox</em>`q̔㏸ƂʒuɓٓIȉéCɔ<em>hoxa</em>NX^[<em>hoxc</em>NX^[ɂĂF߂ꂽ<a href="#R13"><sup>13)</sup></a>i<a href="#F5">}5a</a>jD́CNipblɂF̂̍\@\CقȂ<em>hox</em>NX^[ɂՓIɕۑꂽʂ̋@\ł\D<em>hox</em>`qQ̔Shh̉ɂătB[hobNɂ萧䂳邱ƂĂCNipblɂ<em>shh</em>`q̐̉\lꂽDCShhVOȋjQ܂ɂ菈ɂ鎈ɂ`q̔̕ωNipblmbN_ĚʂƂ͈قȂĂCȂƂC̔ւ̉eƂ_ɂĂ͎vȕWIł͂ȂƗ\zꂽ<a href="#R13"><sup>13)</sup></a>D
@Nipbl͂܂܂ȃ^pNƋĈ`q𐧌䂵Ă邱Ƃ͂łɏqׂDł́C̔<em>hox</em>`q̔ɂĂ͂ǂ̂悤ȕq@\֗^Ă̂낤H@M҂̌ł́CȂƂCfBG[^[̂Ƃ̋pdvł邱Ƃ炩ɂꂽ<a href="#R13"><sup>13)</sup></a>DfBG[^[̂̃TujbĝЂƂłMed12̔mbN_E[utBbVł́CNipblmbN_EƓlɁCřȈޏk݂ꂽD̔ɂ`q̔ւ̉eC3̌u<em>in situ</em>nCu_C[[V@ɂ<em>hoxd</em>NX^[̎ӂ̍\̉͂Ȃǂ́CׂāCNipblmbN_EƂƓľʂi<a href="#F4">}4b</a>C<a href="#F5">}5</a>jDfBG[^[̂NipblƂ̑ݍṕCESזEł͎Ă̂́C̂ɂĂ͖炩ɂĂ炸CM҂̌<em>in vivo</em>ɂ͂߂Ă̏ؖɂȂD
@CNipbl̃p[gi[ƂĂƂLȃRq[Vł邪C̃TujbgłRad21mbN_EƂC`qւ̉eȂǂNipbl邢Med12mbN_ĚʂƂ͕KvȂ<a href="#R13"><sup>13)</sup></a>DRq[V̕ψقɋN^CvCornelia de LangeǌQ͑S̓IɏǏ󂪌ylɑ΂錰ȉe݂ȂƂmĂCƂȂ炩̊֘ÂȂD

<h2></h2>
@F̂̍\͈̐`q̎邢͑gDɂٓIȔdvȋ@\̂ЂƂłDRq[VƂ̊֘AÂɂ肻̕q@\̗傫i݁CɁCCornelia de LangeǌQ̂悤ȃRq[Va̔ǋ@\̉𖾂ɂ̍vƂ́C10Nقǂ̑傫ȐʂłƂD̈CF̗̂̈̂̑ݍp̌`₻ِ̓̌Ɋւ镪q@\ɂẮC_łقƂǂ킩ĂȂDF̗̂̓̈ǂCƂ΁CGnT[Ƃ̕WIƂȂv[^[́Cǂ̂悤ɂČ݂F̂H@_Ci~bNȐF̂̍\̕ω铮͉͂H@ɂ͓RCRq[VNIPBLȂǂ֘AĂ邾낤DC1זExł̉͋Zp␶זEɂF̂̉ZpȂǂ̌ɂCq@\ɖ炩ɂƗ\zD܂܂̂ȂłD

<h2> </h2>
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</ol>
<div class="au-profile">
<h2>҃vtB[</h2>
<span class="author"> FiAkihiko Mutoj</span>
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