Inducible gene deletion in glial cells to study angiogenesis in the central nervous system

Abstract

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.