Abstract
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.
Highlights
Reconstruction of the corticospinal tract (CST) by cell transplantation is one of the main strategies to treat brain injury and stroke
These results indicate that the frontal cortex of E14.5 mouse contains cells that extend their axons along the CST and that these cells express CTIP2
L1CAM is expressed throughout the nervous system and is involved in axon growth and guidance during development, interactions between Schwann cells and axons, FIGURE 2 | Mouse ESC-derived CTIP2:GFP+ cells show characteristics of corticospinal motor neurons (CSMNs). (A) Schematic diagram of the cortical differentiation protocol from mouse embryonic stem cells. (B) Bright-field and CTIP2:GFP images of the floating culture of cell aggregates from day 0 to day 12
Summary
Reconstruction of the corticospinal tract (CST) by cell transplantation is one of the main strategies to treat brain injury and stroke. Previous studies have reported that behavioral improvement was observed after transplantation of the embryonic cerebral cortex in rat models with brain injury or middle cerebral artery occlusion (Plumet et al, 1993; Grabowski et al, 1995; Mattsson et al, 1997; Riolobos et al, 2001). When grafted into the frontal cortex, the induced neurons extend their axons to the corresponding targets and integrate into the host brain (Espuny-Camacho et al, 2013). Reconstruction of the CST by PSC-derived neurons can be a novel therapy for brain injury and stroke
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call