Control of neural stem cell migration by electric fields

Neural stem cells showed strong electrotaxis, evidenced by highly directed migration towards the cathode. Optimal electrotaxis was found to require growth factors and phosphoinositide 3-kinase (PI3-K) signalling, although reduced electrotaxis could be obtained without growth factors at the highest EFs used. After EF exposure, neural stem cell trajectories became much more linear, and a reduction in the number of cell protrusions oriented towards the anode was observed. Also, protrusions initially orienting towards the cathode retracted after the polarity of the EF was reversed, suggesting that EFs could inhibit the extension of anodal protrusions. A simple model of neural stem cell migration was built with only two key parameters, which reproduced accurately neural stem cell migration patterns, and predicted that PI3-K functions in electrotaxis mainly by controlling cell orientation. Finally, wild-type and Pax6-/- embryonic neural stem cells were exposed simultaneously to EFs and contact guidance cues in conflicting orientations. Only wild-type neural stem cells showed significant integrative migratory responses, suggesting that Pax6 is important for integration of diverse guidance cues during cell migration. The results obtained in this thesis show that neural stem cells display strong electrotaxis in vitro, which is accompanied by a qualitative change in the pattern of migration. The results also identify the control of protrusion orientation by EFs as an important element in neural stem cell electrotaxis, contributing insight into the mechanisms of electrotaxis. Finally, these results warrant further studies to assess the possibility of using EFs in brain repair therapies.EThOS - Electronic Theses Online ServiceGBUnited Kingdo