MIR-285-Yki/Mask double-negative feedback loop mediates blood-brain barrier integrity in Drosophila

28Citations
Citations of this article
43Readers
Mendeley users who have this article in their library.

Abstract

The Hippo signaling pathway is highly conserved from Drosophila to mammals and plays a central role inmaintaining organ size and tissue homeostasis. The blood-brain barrier (BBB) physiologically isolates the brain from circulating blood or the hemolymph system, and its integrity is strictly maintained to perform sophisticated neuronal functions. Until now, the underlying mechanisms of subperineurial glia (SPG) growth and BBB maintenance during development are not clear. Here, we report an miR-285-Yorkie (Yki)/Multiple Ankyrin repeats Single KH domain (Mask) double-negative feedback loop that regulates SPG growth and BBB integrity. Flies with a loss of miR-285 have a defective BBB with increased SPG ploidy and disruptive septate junctions. Mechanistically, miR-285 directly targets the Yki cofactor Mask to suppress Yki activity and down-regulates the expression of its downstream target cyclin E, a key regulator of cell cycle. Disturbance of cyclin E expression in SPG causes abnormal endoreplication, which leads to aberrant DNA ploidy and defective septate junctions.Moreover, the expression of miR-285 is increased by knockdown of yki or mask and is decreased with yki overexpression, thus forming a double-negative feedback loop. This regulatory loop is crucial for sustaining an appropriate Yki/Mask activity and cyclin E level to maintain SPG ploidy and BBB integrity. Perturbation of this signaling loop, either by dysregulated miR-285 expression or Yki activity, causes irregular SPG ploidy and BBB disruption. Furthermore, ectopic expression of miR-285 promotes canonical Hippo pathwaymediated apoptosis independent of the p53 or JNK pathway. Collectively, these results reveal an exquisite regulatory mechanism for BBB maintenance through an miR-285-Yki/Mask regulatory circuit.

References Powered by Scopus

Principles of microRNA-target recognition

1932Citations
N/AReaders
Get full text

Development, maintenance and disruption of the blood-brain barrier

1837Citations
N/AReaders
Get full text

Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer

1737Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Drosophila glia: Few cell types and many conserved functions

95Citations
N/AReaders
Get full text

Hippo signaling in cancer: Lessons from Drosophila models

61Citations
N/AReaders
Get full text

Non-coding RNAs in the regulation of blood–brain barrier functions in central nervous system disorders

43Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Li, D., Liu, Y., Pei, C., Zhang, P., Pan, L., Xiao, J., … Bi, X. (2017). MIR-285-Yki/Mask double-negative feedback loop mediates blood-brain barrier integrity in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 114(12), E2365–E2374. https://doi.org/10.1073/pnas.1613233114

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 21

64%

Researcher 7

21%

Professor / Associate Prof. 4

12%

Lecturer / Post doc 1

3%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 14

45%

Agricultural and Biological Sciences 9

29%

Neuroscience 6

19%

Pharmacology, Toxicology and Pharmaceut... 2

6%

Article Metrics

Tooltip
Mentions
News Mentions: 1

Save time finding and organizing research with Mendeley

Sign up for free