Connections among neurons and with target cells enable the plethora of nervous system tasks. The establishment of these connections relies on the specialization of neurons during development, which in the spinal cord is regulated by a family of proteins known as bone morphogenetic proteins (BMPs). The current view is that these proteins trigger a genetically hardwired program that establishes the fate of cells along the dorsoventral axis of the developing spinal cord. However, differentiation of embryonic neurons is also sensitive to electrical activity, which manifests spontaneously in these developing cells. This study will test the hypothesis that a gradient of BMPs across the dorsoventral axis of the nervous system contributes to establish a gradient of calcium-dependent electrical activity in immature spinal neurons that, in turn, regulates neuronal differentiation. A multi-approach study using molecular, pharmacological, biochemical and physiological techniques will be implemented. This investigation may lead to new ways of thinking on how the nervous system develops and will challenge the idea that nervous system development is exclusively genetically driven. Results from this project may identify novel mechanisms of action of BMPs of relevance to many research fields, including developmental biology, neuroscience, stem cells and tissue repair. Overall, this study will contribute to the understanding of how to induce restorative plastic events in a pathological context of loss or impaired nervous system function.
The PI will serve as role model for female and latino students and colleagues. This award will support both graduate and undergraduate students, and the PI will institute a multistep research experience for the Sacramento High School District in the context of outreach activities coordinated by the Center for Biophotonics. The PI will also continue to support international Neuroscience research in developing countries such as Argentina, through participation in argentine scientific meetings and training courses.