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| Neocortical Development |
Research in our laboratory explores how neurons in the neocortex acquire identities that direct unique sensory perceptions and motor controls. Specifically we are interested in the developmental mechanisms of how diverse arrays of neurons are coordinated into high-functional territories. Despite its well-defined anatomical character and functional significance, the mechanisms underlying the precise assembly of distinct functional areas of the cerebral cortex remains largely unknown. Progress has been impeded by our present lack of understanding of the molecular mechanisms by which neuronal subtypes both within cortical layers and across function domains are specified. In our laboratory, we address important questions concerning neocortical development: 1) What are the mechanisms by which diverse cell fate is determined in the neocortex? 2) How are neurons precisely arranged into distinct cortical areas and establish cytoarchitectonic boundaries? 3) To what extent does the refinement of functional areas rely on environmental inputs? To investigate these questions we are utilizing mouse as a model to understand the assembly of functional subdivisions in the mammalian cerebral cortex.
Our recent work has shown that the fate of neocortical neurons is at least in part pre-determined within the progenitor cells. We have found that specification of deep-layer projection neurons is dependent on transcriptional repressor that function cell-autonomously to prevent neurons from acquiring an earlier neuronal phenotype. These results imply cortical intrinsic programs may be co-opted in which neuron fate is established by temporal changes in gene expression. However, in the mature cortex, cortical areas differ in their types and numbers of specific layer neurons along both the anterior-posterior (AP) and medial-lateral (ML) axes. We are exploring the extent to which intrinsic determinants control the specification of neuronal subtypes within discrete regions of the neocortex, as well as the extrinsic influences that refine the boundaries between functional areas of neocortex. To further these studies we employ wide range of techniques including genetic manipulations in mice that will enable conditional loss of gene and cellular functions, recombination mediated cell-lineage tracing, and systematic approaches to identify novel molecules responsible for precise areal specification. Through these studies we wish to understand the mechanistic basis by which unique sensory perceptions and functional circuitries develop in the human neocortex. |
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Fishell G and Hanashima C. Pyramidal neurons grow up and change their mind. Neuron 57. 333-8 (2008)
Hanashima C, et al. The role of Foxg1 and dorsal midline signaling in the generation of Cajal-Retzius subtypes. J Neurosci 27. 11103-11 (2007)
Hanashima C, et al. Foxg1 suppresses early cortical cell fate. Science 303. 56-9 (2004)
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