Central Research Approach: exploiting chromatin-remodeling complexes to study vascular development and maintenance
For the lab’s first decade, we focused on the role of two key ATP-dependent chromatin-remodeling complexes in vascular development: SWI/SNF and NuRD. We first reported that these complexes transcriptionally and antagonistically regulate yolk sac vascular Wnt signaling at midgestation (Griffin and Curtis et al, 2011; Curtis and Griffin, 2012). Further analysis of SWI/SNF mutants at later stages of development revealed that they had defective venous specification due to misregulated expression of the venous transcription factor COUP-TFII (Davis et al, 2013) and defective capillary integrity due to misregulated expression of the serum response factor cofactors MRTFA/B (Menendez and Ong et al, 2017). These studies are important because they were among the first to reveal the contribution of chromatin-remodeling complexes to vascular development, and they established a model for how we could glean interesting genetic and molecular information from vascular phenotypes in chromatin-remodeling complex mutants. Notably, our approach has been tractable and productive because we can frequently attribute the specific phenotypes generated in our mutants to a single misregulated gene or signaling pathway. Therefore, this unbiased approach is revealing genes for which tight transcriptional regulation or timing is essential during vascular development and maintenance.