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

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)647-659
Number of pages13
JournalBiology Open
Volume2
Issue number7
DOIs
StatePublished - Jul 15 2013

Keywords

  • Angiogenesis
  • Blood brain barrier
  • Foxc1
  • Neurovascular development
  • Pericyte

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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  • Cite this

    Siegenthaler, J. A., Choe, Y., Patterson, K. P., Hsieh, I., Li, D., Jaminet, S. C., Daneman, R., Kume, T., Huang, E. J., & Pleasure, S. J. (2013). Foxc1 is required by pericytes during fetal brain angiogenesis. Biology Open, 2(7), 647-659. https://doi.org/10.1242/bio.20135009