Mechanisms That Determine the Internal Environment of the Developing Brain: A Transcriptomic, Functional and Ultrastructural Approach

Liddelow, SA; Dziegielewska, KM; Ek, CJ; Habgood, MD; Bauer, H; Bauer, HC; Lindsay, H; Wakefield, MJ; Strazielle, N; Kratzer, I; Mollgard, K; Ghersi-Egea, JF; Saunders, NR

Author(s): Liddelow, SA; Dziegielewska, KM; Ek, CJ; Habgood, MD; Bauer, H; Bauer, HC; Lindsay, H; Wakefield, MJ; Strazielle, N; Kratzer, I; Mollgard, K; Ghersi-Egea, JF; Saunders, NR;
Details: Publication Year 2013-07-02,Volume 8,Issue #7,Page e65629
Journal Title: PLOS ONE
Publication Type: Journal Article
Abstract: We provide comprehensive identification of embryonic (E15) and adult rat lateral ventricular choroid plexus transcriptome, with focus on junction-associated proteins, ionic influx transporters and channels. Additionally, these data are related to new structural and previously published permeability studies. Results reveal that most genes associated with intercellular junctions are expressed at similar levels at both ages. In total, 32 molecules known to be associated with brain barrier interfaces were identified. Nine claudins showed unaltered expression, while two claudins (6 and 8) were expressed at higher levels in the embryo. Expression levels for most cytoplasmic/regulatory adaptors (10 of 12) were similar at the two ages. A few junctional genes displayed lower expression in embryos, including 5 claudins, occludin and one junctional adhesion molecule. Three gap junction genes were enriched in the embryo. The functional effectiveness of these junctions was assessed using blood-delivered water-soluble tracers at both the light and electron microscopic level: embryo and adult junctions halted movement of both 286Da and 3kDa molecules into the cerebrospinal fluid (CSF). The molecular identities of many ion channel and transporter genes previously reported as important for CSF formation and secretion in the adult were demonstrated in the embryonic choroid plexus (and validated with immunohistochemistry of protein products), but with some major age-related differences in expression. In addition, a large number of previously unidentified ion channel and transporter genes were identified for the first time in plexus epithelium. These results, in addition to data obtained from electron microscopical and physiological permeability experiments in immature brains, indicate that exchange between blood and CSF is mainly transcellular, as well-formed tight junctions restrict movement of small water-soluble molecules from early in development. These data strongly indicate the brain develops within a well-protected internal environment and the exchange between the blood, brain and CSF is transcellular and not through incomplete barriers.
Publisher: PUBLIC LIBRARY SCIENCE
Keywords: BLOOD-CSF BARRIER; OPOSSUM MONODELPHIS-DOMESTICA; BASOLATERAL PLASMA-MEMBRANE; CHOROID-PLEXUS EPITHELIUM; CEREBROSPINAL-FLUID; TIGHT JUNCTIONS; FETAL SHEEP; DIFFERENTIAL EXPRESSION; METABOLIC-ACIDOSIS; GENE-EXPRESSION
Research Division(s): Bioinformatics
Publisher's Version: https://doi.org/10.1371/journal.pone.0065629
Open Access at Publisher's Site: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0065629
Terms of Use/Rights Notice: Copyright: © 2013 Liddelow et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Documents: journal.pone.0065629.pdf - (11.64MB, application/pdf)

Creation Date: 2013-07-02 12:00:00

Last Modified: 2015-09-04 11:23:38