Foxc1 is required by pericytes during fetal brain angiogenesis
Julie A. Siegenthaler,
Youngshik Choe,
Katelin P. Patterson,
Ivy Hsieh,
Dan Li,
Shou-Ching Jaminet,
Richard Daneman,
Tsutomu Kume,
Eric J. Huang,
Samuel J. Pleasure
Affiliations
Julie A. Siegenthaler
Department of Neurology, Programs in Neuroscience and Developmental Biology, Institute for Regenerative Medicine, UC San Francisco, San Francisco, CA 94158, USA
Youngshik Choe
Department of Neurology, Programs in Neuroscience and Developmental Biology, Institute for Regenerative Medicine, UC San Francisco, San Francisco, CA 94158, USA
Katelin P. Patterson
Department of Neurology, Programs in Neuroscience and Developmental Biology, Institute for Regenerative Medicine, UC San Francisco, San Francisco, CA 94158, USA
Ivy Hsieh
Department of Pathology, UC San Francisco, San Francisco, CA 94143, USA
Dan Li
Beth Israel Deaconess Medical Center, Department of Pathology, Harvard School of Medicine, Boston, MA 02215, USA
Shou-Ching Jaminet
Beth Israel Deaconess Medical Center, Department of Pathology, Harvard School of Medicine, Boston, MA 02215, USA
Richard Daneman
Department of Anatomy, UC San Francisco, San Francisco, CA 94143, USA
Tsutomu Kume
Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL 60611, USA
Eric J. Huang
Department of Pathology, UC San Francisco, San Francisco, CA 94143, USA
Samuel J. Pleasure
Department of Neurology, Programs in Neuroscience and Developmental Biology, Institute for Regenerative Medicine, UC San Francisco, San Francisco, CA 94158, USA
Summary Brain pericytes play a critical role in blood vessel stability and blood–brain barrier maturation. Despite this, how brain pericytes function in these different capacities is only beginning to be understood. Here we show that the forkhead transcription factor Foxc1 is expressed by brain pericytes during development and is critical for pericyte regulation of vascular development in the fetal brain. Conditional deletion of Foxc1 from pericytes and vascular smooth muscle cells leads to late-gestation cerebral micro-hemorrhages as well as pericyte and endothelial cell hyperplasia due to increased proliferation of both cell types. Conditional Foxc1 mutants do not have widespread defects in BBB maturation, though focal breakdown of BBB integrity is observed in large, dysplastic vessels. qPCR profiling of brain microvessels isolated from conditional mutants showed alterations in pericyte-expressed proteoglycans while other genes previously implicated in pericyte–endothelial cell interactions were unchanged. Collectively these data point towards an important role for Foxc1 in certain brain pericyte functions (e.g. vessel morphogenesis) but not others (e.g. barriergenesis).
