title: Foxc1 is required by pericytes during fetal brain angiogenesis.
abstract: 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).
authors.affiliation: Department of Neurology, Programs in Neuroscience and Developmental Biology, Institute for Regenerative Medicine, UC San Francisco , San Francisco, CA 94158 , USA ; Present address: Department of Pediatrics, Denver-Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Siegenthaler
authors.forename: Youngshik
authors.initials: Y
authors.lastname: Choe
authors.forename: Katelin P
authors.initials: KP
authors.lastname: Patterson
authors.forename: Ivy
authors.initials: I
authors.lastname: Hsieh
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Shou-Ching
authors.initials: SC
authors.lastname: Jaminet
authors.forename: Richard
authors.initials: R
authors.lastname: Daneman
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kume
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Huang
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Pleasure
keywords: Angiogenesis; Blood brain barrier; Neurovascular development; Pericyte; foxc1