PAX遺伝子群

2012年10月30日 (火) 20:02時点におけるNosumi (トーク | 投稿記録)による版

英:Paired box (Pax) genes

 Pax遺伝子群は動物胎生期に、組織や器官の発生において中心的な役割を果たす遺伝子ファミリーである。脊椎動物ではPax1〜Pax9の9種類が同定されている(図)。Pax遺伝子群は DNA結合ドメインであるペアードドメイン(PD)と呼ばれる領域を共通に持っている。また、Pax遺伝子にはオクタペプチドモチーフ(OP)を持つものや、DNA結合ドメインであるホメオドメイン、もしくはホメオドメインの一部を持つものがある。このような遺伝子配列の違いから、Pax遺伝子群は4つのサブファミリーに分類される。 Pax遺伝子群はヒトマウスに於いて、病気の原因遺伝子として同定されたものが多い。例えば、眼の発生のマスター制御遺伝子であるPAX6は、無虹彩症の原因遺伝子である。

胎生期および生後の神経系におけるPax遺伝子群の発現パターン

 詳細は図およびAllen Brain Atlas[[1]]を参照にされたい。特にPax6は、神経板期(数体節期:マウスE8.5)に、前脳区画および前耳溝以後の菱脳脊髄で発現が開始する。神経管閉鎖後、脳胞期(約30体節期: マウスE10.5)には、終脳背側(将来の大脳皮質領域)、間脳背側(将来の腹側・背側視床)、菱脳脊髄の腹外側で発現する。生後も脳室層、扁桃体視床海馬小脳下垂体などで発現が見られる。中枢神経系以外では、水晶体角膜上皮、網膜神経上皮、嗅上皮、膵臓に発現している。

 
図 Pax遺伝子の構造と発現組織

神経系の発生におけるPax遺伝子群の機能

 Pax遺伝子群は他の転写遺伝子と協調し、神経系の発生初期では細胞の運命決定や脳の領域化 [1][2][3][4][5][6]、発生後期では細胞増殖、細胞移動、細胞分化に関わっている[7][8][9][10][11][12][13]Pax遺伝子群の発現は胎生期において認められるだけではなく、生後および成体脳においても認められる[2][10][11][14][15][16][17][18][19][20]

脳の領域化、細胞の運命決定におけるPax遺伝子群の機能

 Pax遺伝子群の発現は、神経板の形成などの神経発生初期から始まる。神経発生の初期では、シグナルセンターからの情報によって、前後軸背腹軸が決定され、脳の領域化が起こる[21][22]Pax遺伝子群はシグナルセンターから放出されるシグナル分子に反応し[1][23][24][25][26][27][28][29]脳の領域化や細胞の運命決定に寄与することがわかっている[2][4][7][30][31]。Pax6は、菱脳脊髄における運動ニューロン介在ニューロン分化に関して、classI HDタンパクとclassII HDタンパクとの間に正確な境界形成を行うことを通じて菱脳腹側の区画化を制御する[32]。その他Pax6には、前脳のコンパートメント形成、神経路形成(後交連、TPOC、嗅索、視床皮質路)、終脳背側ニューロン分化、小脳顆粒細胞の形成など多岐にわたる役割がある。

神経前駆細胞の増殖および維持におけるPax遺伝子群の機能

 脳の領域化の後、Pax遺伝子群は神経前駆細胞の増殖、維持および分化において重要な役割をはたすことがわかっている。例えば、Pax6は胎生期の脳[33][34][35][36]および成体脳[11][16]において、その発現量依存的に神経前駆細胞の増殖、維持、さらには分化に関わっている。また、Pax6はグリア細胞の一種であるアストロサイトの増殖・分化にも関わっている[37]

細胞移動におけるPax遺伝子群の機能

 複雑な神経回路を構築する過程である神経発生において、細胞移動は時空間的に正確でなければならない。Pax遺伝子群はこの細胞移動に関しても重要な役割を果たす。例えば、Pax3は神経堤細胞の移動に関わっている[38][39]。Pax6は大脳皮質 [13][40]小脳 [41]において細胞移動に関わっている。

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(執筆者:櫻井勝康、吉川貴子、大隅典子 担当編集委員:)