The endothelium is not well understood as a fully functional organ, yet a surprising amount of data exist regarding vascular development during embryogenesis. During mouse development, endothelial cells (ECs) alone make up the vasculature until around halfway through gestation. A large number of knockout and mutant mice exist in which severe defects in the endothelial vasculature at these early stages lead to embryonic lethality. The use of these animals to dissect the genetic interactions with in ECs during development has led to an increased understanding of the endothelium.

The central thread of this chapter is the transcriptional regulation of ECs by members of the Sox gene family, but it also will incorporate relevant information gained from other signaling hierarchies. We have amassed substantial data implicating SOX18 in vascular development (1,2). In situ analysis of Sox18 has demonstrated expression in the condensing mesenchyme underlying the developing hair follicle, in the developing heart, and in the ECs of the vasculature. Mutations in Sox18 lead to mice with defective hair, skin, and vasculature. The vascular defects can be particularly life-threatening, leading to generalized edema due to the leaky vasculature that can result in embryonic or postnatal lethality. Here, we review the data bearing on the molecular and cellular roles of SOX18 and related genes in regulating endothelial phenotype and function.

SOX GENES

Sox genes encode a family of transcription factors, characterized by the presence of a 79 amino acid DNA-binding high mobility group (HMG) domain, similar to that found in mammalian testis-determining factor gene (3). HMG domains can be found in a number of proteins involved in chromatin organization, general transcription and transcriptional regulation.