Spatially Heterogeneous Choroid Plexus Transcriptomes Encode Positional Identity and Contribute to Regional CSF Production

Author(s):Show less -

Lun, Melody P. ^{[1, 2]} ; Johnson, Matthew B. ^[3] ; Broadbelt, Kevin G. ^[1] ; Watanabe, Momoko ^[4] ; Kang, Young-jin ^[4] ; Chau, Kevin F. ^[1] ; Springel, Mark W. ^[1] ; Malesz, Alexandra ^[1] ; Sousa, Andre M. M. ^{[5, 6]} ; Pletikos, Mihovil ^{[5, 6]} ; Adelita, Tai ^{[1, 7]} ; Calicchio, Monica L. ^[1] ; Zhang, Yong ^[8] ; Holtzman, Michael J. ^[8] ; Lidov, Hart G. W. ^[1] ; Sestan, Nenad ^{[5, 6]} ; Steen, Hanno ^[1] ; Monuki, Edwin S. ^[4] ; Lehtinen, Maria K. ^[1]

Affiliation

^[1] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 - USA

^[2] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 - USA

^[3] Boston Childrens Hosp, Div Genet, Boston, MA 02115 - USA

^[4] Univ Calif Irvine, Sch Med, Dept Pathol & Lab Med, Irvine, CA 92697 - USA

^[5] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 - USA

^[6] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 - USA

^[7] Univ Fed Sao Paulo, Dept Biochem, BR-04039 Sao Paulo - Brazil

^[8] Washington Univ, Dept Med, Pulm & Crit Care Med, St Louis, MO 63110 - USA

• Document type: Journal article
• Source: JOURNAL OF NEUROSCIENCE; v. 35, n. 12, p. 4903-4916, MAR 25 2015.
• Web of Science Citations: 29

Abstract

A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the CSF. To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) versus fourth ventricle (hindbrain) choroid plexus. We find that positional identities of mouse, macaque, and human choroid plexi derive from gene expression domains that parallel their axial tissues of origin. We then show that molecular heterogeneity between telencephalic and hindbrain choroid plexi contributes to region-specific, age-dependent protein secretion in vitro. Transcriptome analysis of FACS-purified choroid plexus epithelial cells also predicts their cell-type-specific secretome. Spatial domains with distinct protein expression profiles were observed within each choroid plexus. We propose that regional differences between choroid plexi contribute to dynamic signaling gradients across the mammalian cerebroventricular system. (AU)

• FAPESP's process: 13/24501-9 - Influence of cerebrospinal fluid (CSF) on neural stem cell differentiation
• Grantee: Taís Adelita Morais de Almeida
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate