View Full Text | Abstract |
Article as PDF | Print this Article |
Pubmed | PMC |
PubReader | Export to Citation |
Email Alerts | Open Access |
Exp Neurobiol 2017; 26(2): 71-81
Published online April 30, 2017
https://doi.org/10.5607/en.2017.26.2.71
© The Korean Society for Brain and Neural Sciences
Min Gu Park1,2,3†, Heeyeong Jang5†, Sang-Hoon Lee1,4,5 and C. Justin Lee1,2,3*
1KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, 2Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, 3Center for Glia-Neuron Interaction, Korea Institute of Science and Technology (KIST), Seoul 02792, 4School of Biomedical Engineering, College of Health Science, Korea University, Seoul 02841,5Department of Bio-convergence Engineering, College of Health Science, Korea University, Seoul 02841, Korea
Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-958-6421, FAX: 82-2-958-6919
e-mail: cjl@kist.re.kr
†These authors contributed equally to this work.
Radial glial cells (RGCs) which function as neural stem cells are known to be non-excitable and their proliferation depends on the intracellular calcium (Ca2+) level. It has been well established that Inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release and Ca2+ entry through various Ca2+ channels are involved in the proliferation of RGCs. Furthermore, RGCs line the ventricular wall and are exposed to a shear stress due to a physical contact with the cerebrospinal fluid (CSF). However, little is known about how the Ca2+ entry through mechanosensitive ion channels affects the proliferation of RGCs. Hence, we hypothesized that shear stress due to a flow of CSF boosts the proliferative potential of RGCs possibly via an activation of mechanosensitive Ca2+ channel during the embryonic brain development. Here, we developed a new microfluidic two-dimensional culture system to establish a link between the flow shear stress and the proliferative activity of cultured RGCs. Using this microfluidic device, we successfully visualized the artificial CSF and RGCs in direct contact and found a significant enhancement of proliferative capacity of RGCs in response to increased shear stress. To determine if there are any mechanosensitive ion channels involved, a mechanical stimulation by poking was given to individual RGCs. We found that a poking on radial glial cell induced an increase in intracellular Ca2+ level, which disappeared under the extracellular Ca2+-free condition. Our results suggest that the shear stress by CSF flow possibly activates mechanosensitive Ca2+ channels, which gives rise to a Ca2+ entry which enhances the proliferative capacity of RGCs.
Keywords: Radial glial cell, Shear stress, Mechanosensitive ion channel