Abstract
The cerebral cortical tissue of murine embryo and pluripotent stem cell (PSC)-derived neurons can survive in the brain and extend axons to the spinal cord. For efficient cell integration to the corticospinal tract (CST) after transplantation, the induction or selection of cortical motor neurons is important. However, precise information about the appropriate cell population remains unclear. To address this issue, we isolated cells expressing Neuropilin-1 (NRP1), a major axon guidance molecule receptor during the early developmental stage, from E14.5 mouse embryonic frontal cortex by fluorescence-activated cell sorting. Aggregates of NRP1+ cells gradually expressed subcortical projection neuron markers, Ctip2 and VGluT1, and axon guidance molecule receptors, Robo1 and deleted in colorectal calcinoma (Dcc), in vitro, suggesting that they contained early-stage subcortical projection neurons. We transplanted NRP1+ cells into the frontal cortex of P2 neonatal mice. Compared with grafts derived from NRP1− or unsorted cells, those derived from NRP1+ cells extended a larger number of axons to the spinal cord along the CST. Our data suggest that sorting NRP1+ cells from the embryonic cerebral cortex enriches subcortical projection neurons to reconstruct the CST.
Highlights
Cell-based therapy is a promising treatment for neurodegenerative diseases such as Parkinson’s disease (Lindvall and Hagell, 2000; Doi et al, 2014) and Huntington’s disease (Gallina et al, 2010)
pluripotent stem cell (PSC)-derived neurons survive and improve motor dysfunction (Oki et al, 2012; Shinoyama et al, 2013; Tornero et al, 2013). These findings suggest that embryonic cortical tissue and PSC-derived Neural progenitor cells (NPCs) have the potential to reconstruct the corticospinal tract (CST), but the cell population that extends axons to the spinal cord upon transplantation remains unknown
The cerebral cortex of E14 is divided into four layers that include the cortical plate and the intermediate (IZ), subventricular (SVZ) and ventricular (VZ) zones, and each layer is characterized by specific markers (Figure 1A)
Summary
Cell-based therapy is a promising treatment for neurodegenerative diseases such as Parkinson’s disease (Lindvall and Hagell, 2000; Doi et al, 2014) and Huntington’s disease (Gallina et al, 2010). PSC-derived neurons survive and improve motor dysfunction (Oki et al, 2012; Shinoyama et al, 2013; Tornero et al, 2013). These findings suggest that embryonic cortical tissue and PSC-derived NPCs have the potential to reconstruct the CST, but the cell population that extends axons to the spinal cord upon transplantation remains unknown. To address this issue, we sought a novel cell surface marker for this cell population in the murine embryonic cortex
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