TY - JOUR
T1 - Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila
AU - Kanda, Hiroshi
AU - Shimamura, Rieko
AU - Koizumi-Kitajima, Michiko
AU - Okano, Hideyuki
N1 - Funding Information:
We thank the members of the Okano laboratory for helpful discussions. We thank Takatoshi Iijima for technical support. We would like to thank Douglass Sipp, Tatsushi Igaki, and Masayuki Miura for their comments on the manuscript. We thank Roland Bainton for his comments on the anti-P-gp antibody. We thank Ryu Ueda, Roland Bainton, Andrea Page-McCaw, Dan Kiehart, Doris Brentrup, Deborah Kimbrell, Kei Ito, and Masayuki Miura for kindly sharing materials. We thank the Bloomington Drosophila Stock Center, the National Institute of Genetics Stock Center (NIG-FLY), the Drosophila Genomics and Genetic Resources (DGGR, Kyoto Institute of Technology), and the TRiP at Harvard Medical School (NIH/NIGMS R01-GM084947) for fly stocks. This work was supported in part by JSPS KAKENHI Grant Numbers 23790236, 23122519, 25122714, 26111722, 26670095, 17K07116 (to H.K.). H.K was also supported in part by Keio Gijuku Academic Development Funds, the Brain Science Foundation, the Kanae Foundation for the Promotion of Medical Science, the Takeda Science Foundation, the Mitsubishi Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, and the Inamori Foundation. H.K. designed the study, conducted most of the experiments, analyzed the data, and wrote the manuscript. R.S. and M.K-K. supported the experiments. H.K. and H.O. oversaw the project. The authors declare no competing financial interests.
Funding Information:
We thank the members of the Okano laboratory for helpful discussions. We thank Takatoshi Iijima for technical support. We would like to thank Douglass Sipp, Tatsushi Igaki, and Masayuki Miura for their comments on the manuscript. We thank Roland Bainton for his comments on the anti-P-gp antibody. We thank Ryu Ueda, Roland Bainton, Andrea Page-McCaw, Dan Kiehart, Doris Brentrup, Deborah Kimbrell, Kei Ito, and Masayuki Miura for kindly sharing materials. We thank the Bloomington Drosophila Stock Center, the National Institute of Genetics Stock Center (NIG-FLY), the Drosophila Genomics and Genetic Resources (DGGR, Kyoto Institute of Technology), and the TRiP at Harvard Medical School (NIH/ NIGMS R01-GM084947 ) for fly stocks. This work was supported in part by JSPS KAKENHI Grant Numbers 23790236 , 23122519 , 25122714 , 26111722 , 26670095 , 17K07116 (to H.K.). H.K was also supported in part by Keio Gijuku Academic Development Funds , the Brain Science Foundation , the Kanae Foundation for the Promotion of Medical Science, the Takeda Science Foundation , the Mitsubishi Foundation , the Mochida Memorial Foundation for Medical and Pharmaceutical Research, and the Inamori Foundation .
Publisher Copyright:
© 2019 The Author(s)
PY - 2019/6/28
Y1 - 2019/6/28
N2 - The blood-brain barrier (BBB) is an essential system that isolates the central nervous system from the internal environment. Increasing evidence has begun to reveal the molecules that are required for BBB integrity. However, how these components are regulated remains unclear. Here we report that a matrix metalloproteinase, Mmp2, is essential for the establishment of the BBB in Drosophila. In the absence of mmp2, the BBB becomes leaky, which allows the tracer to penetrate the brain. Moreover, the expression pattern of a junctional component, Neuroglian, is altered. We also find that the regulation of the amounts of particular extracellular matrix components is critical for BBB establishment. Furthermore, the process of mesenchymal-epithelial transition of BBB-forming cells is perturbed in the absence of Mmp2. These data indicate that the presence of Mmp(s), which is typically considered to be a risk factor for BBB degradation, is essential for BBB integrity in Drosophila. Biological Sciences; Molecular Biology; Cell Biology
AB - The blood-brain barrier (BBB) is an essential system that isolates the central nervous system from the internal environment. Increasing evidence has begun to reveal the molecules that are required for BBB integrity. However, how these components are regulated remains unclear. Here we report that a matrix metalloproteinase, Mmp2, is essential for the establishment of the BBB in Drosophila. In the absence of mmp2, the BBB becomes leaky, which allows the tracer to penetrate the brain. Moreover, the expression pattern of a junctional component, Neuroglian, is altered. We also find that the regulation of the amounts of particular extracellular matrix components is critical for BBB establishment. Furthermore, the process of mesenchymal-epithelial transition of BBB-forming cells is perturbed in the absence of Mmp2. These data indicate that the presence of Mmp(s), which is typically considered to be a risk factor for BBB degradation, is essential for BBB integrity in Drosophila. Biological Sciences; Molecular Biology; Cell Biology
KW - Biological Sciences
KW - Cell Biology
KW - Molecular Biology
UR - http://www.scopus.com/inward/record.url?scp=85066922175&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066922175&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2019.05.027
DO - 10.1016/j.isci.2019.05.027
M3 - Article
AN - SCOPUS:85066922175
VL - 16
SP - 218
EP - 229
JO - iScience
JF - iScience
SN - 2589-0042
ER -