尖端細胞の専門化によって活性化される脳特有の血管新生機構

Giel Schevenels¹, Pauline Cabochette¹, Michelle America¹

¹Laboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles (ULB), Gosselies, Belgium.

Nature

|April 3, 2024

まとめ

脳の血管の発達は,Mmp25発現を制御するWnt7a/b信号に依存しています. このメカニズムは,脳内の内皮細胞の移動を誘導します.

科学分野:

神経科学
発達生物学
血管生物学

背景:

脊椎動物の臓器には特定の機能に合わせたユニークな血管があります
これらの臓器特有の血管の発達は,一般的な血管化プロセスとは独立していると考えられています.

研究の目的:

脳特有の血管形成 (血管新生) の基礎にある分子メカニズムを調査する.
器官型血管の専門化は血管化プロセスとは無関係であるという考えに異議を唱える.

主な方法:

ゼブラフィッシュのCRISPR-Cas9変異を活用して遺伝子機能を研究した.
脳血管新生における Wnt7a/b リガンドとMmp25の役割を調査した.
Mmp25によるコラーゲンIV鎖の分裂を分析した.
塩基底膜への遺伝的干渉の影響を調べました

主要な成果:

Mmp25発現による脳血管新生を制御するWnt7a/b依存の経路を特定した.
Mmp25の肝臓底膜の内皮細胞移動における重要な役割が示された.
Mmp25は特定のコラーゲンIV鎖を裂き,脳への侵入を容易にする.
Wnt-β-カタニン依存性血管新生を阻害し血液-脳バリアに欠陥が生じる

結論:

局所的なシグナル (Wnt7a/b) と特定のプロテアゼ (Mmp25) によって制御される臓器特有の血管新生のための新しいメカニズムを明らかにした.
細胞外マトリックスと内皮細胞の相互作用が脳血管化の重要性を強調した.
臓器型制御と血管新生と血脳障壁の整合性との関連が確認されました

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