グリッドロック信号経路は,最初の胚動脈を形成する
1Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown 02129, USA.
Nature
|November 9, 2001
まとめ
この研究は,ゼブラフィッシュの混合前駆体から動脈と静脈がどのように形成されるかを明らかにしています. ノッチ・シグナル伝達によって調節される,グリッドロック (grl) と呼ばれる遺伝子は,これらの細胞を動脈または静脈になるように導く.
科学分野:
- 発達生物学 発達生物学について
- 血管生物学 血管生物学
- 遺伝学 遺伝学とは
背景:
- 動脈と静脈は,異なる形態的,機能的,分子的な特徴を備えています.
- 血管新生の間に動脈静脈の分化を確立する発達メカニズムは,ほとんど不明のままである.
研究 の 目的:
- 胚の発達中の初期動脈静脈細胞運命を決定する分子経路を調査する.
- 血管パターンの確立におけるグリッドロック (grl) 遺伝子とNotchシグナル伝達の役割を明らかにする.
主な方法:
- アンジオブラスト前駆者の運命を追跡するために,ゼブラフィッシュの胚における系統追跡.
- 動脈 (エフリン-B2) と静脈 (エフB4受容体) マーカーの遺伝子発現分析.
- 遺伝子操作は,変異とモルフォリノアンチセンスを用いて,グリッドロック (grl) とノッチシグナル伝達 (Su(H)) を変化させる.
主要な成果:
- 動脈と静脈のための血管芽細胞前駆体は,最初は空間的に混ざり合っている.
- Gridlock (grl) 発現は動脈前駆者に限定され,動脈形成に不可欠です.
- 減少したGRLまたはNotchシグナリングは,マーカー表現の変化によって証明される動脈から静脈への運命変換につながる.
結論:
- Notch-gridlock (grl) 信号伝達経路は,胚の早期血管発達中の動脈細胞の運命を決定する.
- この経路は,当初未関与の前駆体から特定の動脈対静脈細胞運命決定を判断するように見える.
関連する概念動画
01:56Gastrulation
65.7K
Gastrulation establishes the three primary tissues of an embryo: the ectoderm, mesoderm, and endoderm. This developmental process relies on a series of intricate cellular movements, which in humans transforms a flat, “bilaminar disc” composed of two cell sheets into a three-tiered structure. In the resulting embryo, the endoderm serves as the bottom layer, and stacked directly above it is the intermediate mesoderm, and then the uppermost ectoderm. Respectively, these tissue strata...
65.7K
01:30Neurulation
45.0K
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
45.0K
01:51Determination
20.6K
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
20.6K
01:07Development of Blood Vessels
1.3K
The development of the vascular system in a fetus is a complex and intricate process that begins as early as 15 to 16 days post-conception. This process starts outside the embryo, specifically in the mesoderm of the yolk sac, chorion, and connecting stalk. Approximately two days later, the formation of blood vessels occurs within the embryo itself.
The initial formation of this system is facilitated by the small amount of yolk present in the ovum and yolk sac. Blood vessels originate from...
The initial formation of this system is facilitated by the small amount of yolk present in the ovum and yolk sac. Blood vessels originate from...
1.3K
01:10Mechanism of Angiogenesis
6.6K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
6.6K
01:24Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K