Pharmacological Modulation of Neurite Outgrowth in Human Neural Progenitor Cells by Inhibiting Non-muscle Myosin II

Studies on neural development and neuronal regeneration after injury are mainly based animal models. The establishment of pluripotent stem cell (PSC) technology, however, opened new perspectives for better understanding these processes in human models by providing unlimited source hard-to-obtain tissues. Here, we aimed at identifying the molecular factors that confine modulate an early step regeneration, formation neurites progenitor cells (NPCs). Enhanced green fluorescent protein (eGFP) was stably expressed NPCs differentiated from embryonic induced PSC lines, neurite outgrowth investigated under normal injury-related conditions using a high-content screening system. We found inhibitors non-muscle myosin II (NMII), blebbistatin its novel, non-toxic derivatives, initiated extensive NPCs. extracellular matrix components strongly influenced rate but NMII were able to override inhibitory effect restrictive environment. Non-additive stimulatory generation also detected inhibition Rho-associated, coiled-coil-containing kinase 1 (ROCK1), upstream regulator NMII. In contrast, c-Jun N-terminal kinases (JNKs) had only negligible effect, suggesting ROCK1 signal is dominantly manifested actomyosin activity. addition reliable cell-based vitro model intrinsic mechanisms environmental responsible impeded axonal humans, our results demonstrate important pharmacological targets augmentation level. These studies may open novel more effective treatments therapies various neurodegenerative disorders.