The development of the nervous system involves the specification of neural progenitors and eventual differentiation into mature neurons. Each step in this process is achieved through changes in cell fate and is coordinated by precise expression and function of transcription factors (TFs). Sox proteins are a large family of TFs that along with partner proteins, regulate the production, differentiation, and maturation of cells in the nervous system. Previous studies have shown that Sox11, a member of the SoxC family, is dynamically expressed in Xenopus laevis (frog) and Mus musculus (mouse) neural development and plays similar roles in promoting neuronal differentiation in each system. While deficits in Sox11 function have been implicated in neurodevelopmental disorders and malformations in the cerebral cortex and spinal cord, molecular mechanisms of Sox11 function remain poorly understood. To address this, the F99 phase of this proposal will investigate Sox11's diverse role in neural development using two models - frog and mouse - in order to characterize Sox11 function in distinct models. Results from these studies will provide critical information about neural development and chages in TF function over evolutionary time, and may provide information on Sox11's potential role in neural injury and plasticity and, possibly, even cancer. Completion of the F99 phase sets a strong intellectual, technical and professional foundation for the postdoctoral (K00) phase of this award. During the K00 phase, training in understanding how neuronal identity is generated and whether deficits may lead to neurodevelopmental disorders will develop knowledge, expertise, and skills essential to becoming an independent investigator.
The F99 phase of this proposal will investigate Sox11's diverse role in neural development using two models Xenopus laevis (frog) and Mus musculus (mouse). Results from this study have the potential to inform studies not only regarding Sox11's role in neural development, but also cancer research and neural injury and repair, given that Sox11 is implicated as an essential protein in these fields. Completion of the F99 phase will provide training in intellectual, technical and professional skillsets in preparation for and transition to the postdoctoral (K00) phase of this award.
