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有顎脊椎動物における眼窩側頭域の発生と進化

黒田, 春也 クロダ, シュンヤ 神戸大学

2022.03.25

概要

脊椎動物の頭部筋骨格系をもたらす間葉細胞は、中胚葉と神経堤細胞によって構成される。有顎脊椎動物において、咽頭胚期までに成立した中胚葉と神経堤細胞の分布境界は、一部の細胞タイプを除いて、その後の発生過程においても互いにほとんど混ざり合うことなく、頭部筋骨格系の構成要素の中に発生由来の分布パターンとして維持される傾向がある。しかし、発生期に成立した中胚葉・神経堤細胞境界が、筋骨格系の発生や形態的相同性とどのような関係性にあるのかについては、ほとんど明らかになっていない。そこで本論文では、脊椎動物で形態的相同性が非常によく保存されていることで知られる外眼筋の形態形成と中胚葉・神経堤細胞境界との関係性について、軟骨魚類のトラザメと哺乳類のマウスといった有顎脊椎動物のなかで最も系統的に隔たった二種間の比較を通じて迫った。第1章では、このような研究背景について記述した。

第2章では、トラザメ胚頭部に一過的に形成され、頭腔とよばれる上皮性体腔を利用し、生体色素の微量注入による頭部中胚葉の細胞系譜解析について記述した。これにより、技術的な困難のために知見が不足していた軟骨魚類頭部における中胚葉由来の胚環境の分布を明らかにすることができた。その結果、頭腔が外眼筋の筋線維だけではなく、その結合組織の一部にも分化することを明らかにした。よってトラザメの外眼筋のうち直筋要素は中胚葉・神経堤細胞境界に形成される骨格筋であることが示唆された。

第3章では、遺伝子改変マウスを用いた遺伝的細胞系譜解析を記述した。まず、マウス胚において外眼筋を含む眼裔側頭域の中胚葉・神経堤細胞境界の分布を詳細に再記載し、哺乳類で直筋の起始となっている視交叉下翼とよばれる骨格の発生的・進化的起源について鏃論した。その結果、これまで相同性が明らかになっていなかった哺乳類の視交叉下翼が、竜弓類の上梁軟骨と相同であることを強く示す証拠が得られた。これによって、直筋の起始における中胚葉性の発生環境が哺乳類に固有であるという、これまでの仮説が否定された。

第4章では、第2章と第3章の実験から得られた結果を比較することにより、トラザメとマウスの眼裔側頭域の発生過程にみられる共通点と相違点について記述した。共通していたのは、トラザメとマウスの直筋群がいずれも頭部筋としては例外的に中胚葉由来の結合組織を含み、中胚葉・神経堤細胞境界という特殊な領域を発生環境としていることが示唆されたことである。一方相違点としては、咽頭胚期以降の頭部形態形成において中胚葉・神経堤細胞境界が動物種特異的な変形パターンを示し、マウスではトラザメよりも吻側へこの境界が広がっていたことが挙げられる。以上より、外眼筋のうち直筋要素は中胚葉・神経堤細胞境界という骨格筋の中でも特殊な発生環境に拘束されており、この発生拘束によって動物種ごとに異なる中胚葉・神経堤細胞境界の最終的な分布に従い、直筋の近位付着部位の形態的多様性が生じると結論した。

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