A fundamental question in biology is how development of the elaborately organized mammalian brain is orchestrated. Current knowledge suggests that the pattern formation during brain development is guided by a variety of signals including cell adhesive interactions and diffusible neurotrophic factors present within the local microenvironment. The relative contributions of these elements and the number of permutations of each type of signal are unknown. To develop a better understanding of the movement and differentiation of neural stem cells and neural progenitor cells (NPCs) in vivo, we are employing cell culture systems to provide quantitative data that may facilitate modeling these developmental processes.
In our studies we are testing the hypothesis that individual cells in a NPC population are diverse in their capability of responding to their microenvironment by migration and differentiation. As a corollary to this hypothesis, we are testing whether NPCs respond with different behaviors to unique combinations of signals from diffusible factors and preformed distributions of extracellular matrix (ECM) proteins. We have found that manipulation of a combination of physical, chemical and biological cues produces a dynamic environment for specific cellular activities such as directed growth and differentiation of neural progenitor cells. These results may have important application in developing novel experimental strategies for neural regeneration.
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