[Abstract Title]. - Society for Neuroscience

Disclosures: V. Manda , None; R.K. Mittapalli, None; P.R. Lockman, DOD: BC050006, B.
Research Grant (principal investigator, collaborator or consultant and pending grants as well as
grants already received); Q.R. Smith, None.
Poster
287. Blood Brain Barrier and CSF
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 287.2/QQ56
Topic: E.09.c. Blood brain barrier
Support: Myelin Repair Foundation
NIH Grant NS045621
Title: Molecular mechansims regulating blood-brain barrier formation during development
Authors: *R. DANEMAN, D. AGALLIU, L. ZHOU, B. A. BARRES;
Stanford Univ., Stanford, CA
Abstract: The vasculature of the central nervous system forms a barrier, not found in other
tissues, that limits the flow of molecules and ions from the blood into the brain. This blood-brain
barrier (BBB) is crucial for maintaining brain homeostasis and for blocking the flow of toxins,
pathogens, and even the bodies own immune system into the brain. Despite its importance, little
is known about the molecular mechanisms regulating the development of this crucial barrier. In
this study, we perform comparative microarray analysis to determine the blood-brain barrier
specific transcriptome. To accomplish this we utilized fluorescent associated cell sorting to
purify endothelial cells from the brain, liver and lungs of Tie2GFP transgenic mice. Using cDNA
microarrays to analyze the mRNA expressed in different cell populations we are able to make
several important comparisons. First, we have compared the transcriptional profile of endothelial
cells (GFP+) with CNS parenchymal cells (GFP-), to generate a data set of vascular specific
genes. Second, comparison of transcriptional profile of brain GFP+ cells, with liver and lung
GFP+ cells has allowed us to generate a comprehensive list of transcripts that are specific to the
BBB. Finally, by isolating GFP+ cells from the brains of Tie2GFP mice of different ages, we are
able to elucidate the transcriptional changes that occur during the development of the BBB. This
analysis has identified that Wnt/beta-catenin signaling is enriched in CNS endothelial cells
compared with the endothelial cells from the liver and lung. We further demonstrate that
Wnt/beta-catenin signaling is necessary for proper CNS angiogenesis and also regulates the
expression of BBB specific transporters in CNS endothelial cells. Taken together these data