Two major goals of developmental neurobiology are to identify the germinal cells which form the central nervous system and to characterize the cellular and molecular mechanisms by which these cells generate the proper numbers and types of neurons. This proposal represents our ongoing efforts to precisely define the molecular and morphological identity of each neural precursor type present in the mammalian neocortical wall. In this project, the Haydar lab at Boston University teams with the Sestan lab at Yale University to perform genetic fate mapping of precursor populations, followed by next generation RNA sequencing at both the bulk and single cell level. Several differentially expressed genes have already been identified which modulate proliferation or neuronal output from specific precursor groups, and one new gene target has been engineered into a new fate mapping tool useful for further subdivision of cell lineages. Altogether, experiments in this project will identfy precursor cell types and subtypes with unprecedented clarity and isolate key differentially expressed genes. These cell type- specific target genes will then be tested in a series of in vivo experiments for their role(s) in neurogenesis and neuronal positioning.
How the growing list of neural precursor cells coordinate to provide the rich diversity of neurons in the cerebral cortex is not well understood. This information is important for understanding normal brain development and for understanding how changes in neural precursors lead to developmental disorders such as Down syndrome, epilepsy and autism. This project uses new methods of genetic labeling, cell capture and RNA sequencing in wild-type mice to isolate the molecular fingerprint of each type of neural precursor present in the developing brain. Genes which distinguish each cell types will be analyzed for their roles in cortical growth.
|Mi, Da; Li, Zhen; Lim, Lynette et al. (2018) Early emergence of cortical interneuron diversity in the mouse embryo. Science 360:81-85|
|Silbereis, John C; Pochareddy, Sirisha; Zhu, Ying et al. (2016) The Cellular and Molecular Landscapes of the Developing Human Central Nervous System. Neuron 89:248-68|