Cell migration is an important part of many normal and pathological morphogenetic processes, including central nervous system (CNS) development. Neural progenitors are created in proliferative zones within the brain and migrate to specific destinations guided by various extracellular cues and neurotrophic factors (1, 2). In addition, some developmental neurotoxicants have been shown to interfere with the migratory behavior of neural stem cells (e.g., ref. 3). The ability to identify cell migration stimulators and inhibitors can be useful for developing novel neuroregenerative therapies, identifying neurotoxicants, and testing drug candidates for safety.
To meet that need, ArunA and the team at Platypus Technologies are developing an assay for identifying cell migration stimulators and inhibitors using ArunA’s hNP1™ human neural progenitors and Platypus’ novel HTS-compatible 96-well based cell migration assay platform (Oris™ Cell Migration Assay). Early results demonstrate that cytochalasin D, an actin polymerization inhibitor, can block hNP1™ migration. Our preliminary results also show that certain growth factors, singly and in combination, can have potent chemokinetic effects on hNP1™ migration. Hence, this combination of the Oris™ platform and ArunA’s neural stem cells will provide a powerful tool to readily identify stimulators and inhibitors of neural progenitor migration.
Even as further development of this assay continues, our progress to date will be presented in poster format (ID# 2089/B409) at the American Society for Cell Biology meeting in Philadelphia, PA on December 14th 2010.
(1) Marín O, Rubenstein JL. (2003) Cell migration in the forebrain. Annual Review of Neuroscience 26:441-83.
(2) Marín O, et al. (2003) Directional guidance of interneuron migration to the cerebral cortex relies on subcortical Slit1/2-independent repulsion and cortical attraction. Development. 130(9):1889-901.
(3) Moors M, et al. (2009) Human neurospheres as three-dimensional cellular systems for developmental neurotoxicity testing. Environmental Health Perspectives 117(7):1131-8.