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| Status |
Public on Dec 31, 2013 |
| Title |
Homeostatic interactions between chemoprotective functions at the blood-brain barrier |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by array
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| Summary |
The blood-brain barrier (BBB) is an evolutionary conserved tissue interface that possesses potent chemical protection properties functioning to strictly modulate the central nervous system (CNS) microenvironment. These same properties, including tight cellular junctions and efflux transporters, also limit access of CNS-active pharmaceuticals. For this reason, understanding the molecular mechanisms that regulate BBB chemical protection is of great biomedical interest. The BBB of Drosophila consists of two surface glia layers that completely surround the brain. This tissue interface contains both “tight” cellular junctions (termed septate junctions) and drug efflux transporters; thus, the Drosophila BBB can potentially serve as a model for understanding complex regulation of BBB physiology.
In this study, we show reciprocal compensatory responses following disruption of critical BBB genes: deletion of the septate junction regulator Moody causes increased drug efflux and up-regulation of the P-glycoprotein ortholog Mdr65; conversely, disruption of Mdr65 expression causes increased septate junction tightness and up-regulation of Moody. We reveal these homeostatic interactions with physiologic observations, gene expression data, and anatomical images of the BBB surface. Whole brain microarray data point to responses that are consistent with our physiologic observations and these responses are likely localized to the BBB. To our knowledge, this is the first observation of a reciprocal compensatory interaction at a tissue barrier. Furthermore, this study paves the way for future studies elucidating the direct pathways that link GPCR signaling and drug transporter regulation at the BBB.
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| Overall design |
The main comparisons are between WT_new, C17 (Moody null), and PMdr65 (Mdr65 null). Since WT_new were processed on a different day than C17 and PMdr65, we also included another WT sample (WT_old) to control for genes that change depending on batch effects. Since the mutants are also in a different genetic background than WT, we also included a control that is in a similar background (UAS_control).
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| Contributor(s) |
DeSalvo MK, Bainton RJ |
| Citation missing |
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| Submission date |
May 01, 2013 |
| Last update date |
May 04, 2018 |
| Contact name |
Michael DeSalvo |
| E-mail(s) |
[email protected]
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| Organization name |
UC San Francisco
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| Department |
Department of Anesthesia
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| Lab |
Roland Bainton
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| Street address |
600 16 St Box 2200
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158-2200 |
| Country |
USA |
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| Platforms (1) |
| GPL1322 |
[Drosophila_2] Affymetrix Drosophila Genome 2.0 Array |
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| Samples (17)
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| GSM1132144 |
Canton S, wildtype, whole brain, new, rep1 |
| GSM1132145 |
Canton S, wildtype, whole brain, new, rep2 |
| GSM1132146 |
Canton S, wildtype, whole brain, new, rep3 |
| GSM1132147 |
Canton S, wildtype, whole brain, old rep1 |
| GSM1132148 |
Canton S, wildtype, whole brain, old rep2 |
| GSM1132149 |
Canton S, wildtype, whole brain, old rep3 |
| GSM1132150 |
Canton S, wildtype, whole brain, old rep4 |
| GSM1132151 |
Canton S, wildtype, whole brain, old rep5 |
| GSM1132152 |
PMdr65, Mdr65 null, whole brain, rep1 |
| GSM1132153 |
PMdr65, Mdr65 null, whole brain, rep2 |
| GSM1132154 |
PMdr65, Mdr65 null, whole brain, rep3 |
| GSM1132155 |
UAS-Mdr65-RNAi, whole brain, rep1 |
| GSM1132156 |
UAS-Mdr65-RNAi, whole brain, rep2 |
| GSM1132157 |
UAS-Mdr65-RNAi, whole brain, rep3 |
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| Relations |
| BioProject |
PRJNA200957 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46550_RAW.tar |
33.7 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE46550_normalized_unfiltered_matrix.txt.gz |
585.6 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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