L1CAM is a marker for isolating corticospinal motor neurons in the developing brain
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PROVIDER: PRJNA547745 | ENA |
REPOSITORIES: ENA
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Project description:The cerebral cortical tissue of murine embryo and pluripotent stem cell-derived neurons can survive in adult brain and extend axons to the spinal cord. These features suggest that cell transplantation can be a strategy to reconstruct the corticospinal tract (CST). It is unknown, however, which cell population makes for safe and effective donor cells. To address this issue, we grafted the cerebral cortex of E14.5 mouse to the brain of adult mouse and found that the cells in the graft extending axons along the CST expressed CTIP2. By using CTIP2:GFP knockin mouse embryonic stem cells, we identified L1CAM as a cell surface marker to enrich CTIP2+ cells. We sorted L1CAM+ cells from E14.5 mouse brain and confirmed that they extended a larger number of axons along the CST compared to L1CAM- cells. Our results suggest that sorting L1CAM+ cells from the embryonic cerebral cortex enriches subcortical projection neurons to reconstruct the CST.
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Project description:Molecular mechanisms over differentiation and differential axonal targeting of distinct neuron subtypes in the cerebral cortex are beginning to be elucidated. These studies have focused on controls that specifically distinguish one subtype of neocortical projection neurons, e.g. corticospinal motor neurons (CSMN), from closely related corticothalamic projection neurons (CThPN) or intracortical callosal projection neurons (CPN). CSMN are located in layer V of the neocortex and make synaptic connections to motor output circuitry in the spinal cord and brainstem. CSMN axons form the corticospinal tract (CST), which is the major motor output pathway from the motor cortex and critically controls voluntary movement. CSMN somatotopically and precisely target specific segments along the rostrocaudal axis of the spinal cord, the molecular basis for which remains unknown. We used microarrays to examine gene expression differences between two CSMN subpopulations that target different levels of the spinal cord - CSMN-C (which extend axons to the brainstem and cervical spinal cord) and CSMN-L (which preferrrentially extend axons to the thoracic and lumbar spinal cord). We compared CSMN-C vs CSMN-L gene expression at 3 critical developmental time points (previously described in Arlotta et a., 2005)
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Project description:The cerebral cortical tissue of murine embryo and pluripotent stem cell-derived neurons can survive in the adult brain and extend axons to the spinal cord. These features suggest that cell transplantation can be a strategy to reconstruct the corticospinal tract (CST). It is unknown, however, which cell population makes for safe and effective donor cells. To address this issue, we grafted the cerebral cortex of E14.5 mouse to the brain of adult mice and found that the cells in the graft extending axons along the CST expressed CTIP2. By using CTIP2:GFP knock-in mouse embryonic stem cells (mESCs), we identified L1CAM as a cell surface marker to enrich CTIP2+ cells. We sorted L1CAM+ cells from E14.5 mouse brain and confirmed that they extended a larger number of axons along the CST compared to L1CAM- cells. Our results suggest that sorting L1CAM+ cells from the embryonic cerebral cortex enriches subcortical projection neurons to reconstruct the CST.
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