Lee Hye Shin, McCarty Joseph H
Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Methods Mol Biol. 2014;1135:261-74. doi: 10.1007/978-1-4939-0320-7_22.
Most organs and tissues of the vertebrate body harbor elaborate network of blood vessels with diverse functions that are determined, in part, by cues within the local environment (Warren and Iruela-Arispe, Curr Opin Hematol 17:213-218, 2010). How vascular endothelial cells decipher these cues to promote normal blood vessel development and physiology remains largely uncharacterized. In this review, we will focus on genetic strategies to analyze glial regulation of blood vessel growth and sprouting within the microenvironment of the retina, a component of the central nervous system (CNS) that contains a complex web of blood vessels with many unique features, including a blood-retinal barrier (Abbott et al., Nat Rev Neurosci 7:41-53, 2006). Blood vessels promote retinal development and homeostasis and alterations in vascular functions can lead to various developmental and adult-onset retinal pathologies (Fruttiger, Angiogenesis 10:77-88, 2007). How glial cells control retinal endothelial cell growth and sprouting remains largely uncharacterized. We will detail methodologies involving inducible Cre-lox technologies to acutely ablate genes of interest in CNS glial cells. These methods allow for precise spatial and temporal regulation of gene expression to study how glial cells in the retinal microenvironment control angiogenesis and blood-retinal barrier development.
脊椎动物身体的大多数器官和组织都有复杂的血管网络,其功能多样,部分由局部环境中的信号决定(沃伦和伊鲁埃拉 - 阿里斯佩,《血液学当前观点》17:213 - 218,2010年)。血管内皮细胞如何解读这些信号以促进正常血管发育和生理功能,在很大程度上仍不清楚。在本综述中,我们将聚焦于遗传策略,以分析在视网膜微环境中神经胶质细胞对血管生长和出芽的调控,视网膜是中枢神经系统(CNS)的一个组成部分,其包含一个具有许多独特特征的复杂血管网络,包括血视网膜屏障(阿博特等人,《自然神经科学综述》7:41 - 53,2006年)。血管促进视网膜发育和稳态,血管功能的改变可导致各种发育性和成人期视网膜病变(弗鲁蒂格,《血管生成》10:77 - 88,2007年)。神经胶质细胞如何控制视网膜内皮细胞生长和出芽,在很大程度上仍不清楚。我们将详细介绍涉及诱导型Cre-lox技术的方法,以急性敲除中枢神经系统神经胶质细胞中感兴趣的基因。这些方法允许对基因表达进行精确的空间和时间调控,以研究视网膜微环境中的神经胶质细胞如何控制血管生成和血视网膜屏障发育。