Intermediate neuronal progenitors in neocortical development

Seattle Children'S Hospital, Seattle WA

Investigators

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Abstract

DESCRIPTION (provided by applicant): Intermediate neurogenic progenitors (INPs) are a relatively new type of neocortical progenitor cells whose properties, daughter neuron fates, and functions in the regulation of neurogenesis remain unclear. This project will characterize molecular and cellular properties of INPs, define their contribution to cortical areas and layers, and study the regulation of INPs by intrinsic and extrinsic factors. The central hypothesis of this project is that INPs regulate not only overall neurogenesis, but also more subtle aspects of neuron differentiation such as regional identity and laminar fate. These studies will be accomplished using a variety of mouse alleles, including a novel genetic lineage tracing system to identify cortical neurons derived from INP cohorts. The first Aim of this project is to characterize the INP transcriptome, and define proliferative and clonal properties of INPs. The second Aim is to determine the contribution of INP daughter neurons to cortical areas, layers, and cell types. The third Aim is to determine how Eomes, a transcription factor that is specifically expressed in INPs, regulates molecular and developmental properties of INPs. The fourth Aim is to determine how fibroblast growth factor signaling affects INP proliferation and differentiation. Together, these focused studies will provide a coherent understanding of INPs, their roles in corticogenesis, and their possible contributions to neurodevelopmental disorders and therapies. Ultimately, our understanding of diseases such as autism and intellectual disability will be advanced, as will our ability to better diagnose and treat these disorders.