FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation.
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There was no co-localisation of FoxP1 with any interneuron markers.In summary, we show that FoxP1 labels MSN precursors prior to the expression of DARPP-32 during normal development, and in addition suggest that FoxP1 labels a sub-population of MSNs that are not co-labelled by DARPP-32.We demonstrate the utility of FoxP1 to label MSNs in vitro and following neural transplantation, and show that FoxP1 is required for DARPP-32 positive MSN differentiation in vitro.
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PubMed Central - PubMed
Affiliation: Brain Repair Group, Sir Martin Evans Building, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, United Kingdom.
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f0025: FoxP1 expression post-transplantation.Following transplantation of mouse WGE-derived precursors into the adult mouse quinolinic acid-lesioned striatum, FoxP1 protein (brown) is shown at 4 weeks post-transplant (A).Human fetal WGE-derived precursors transplanted into the adult rat quinolinic acid-lesioned striatum identified FoxP1 positive cells (green) at 20 weeks post transplantation (B). Scale bar (A) = 100 μm. Mentions: The ultimate preclinical test for cells differentiated to an MSN phenotype for a therapeutic purpose is to transplant them into an animal model of HD. Therefore, for FoxP1 to be a useful marker in this context, it must continue to be expressed following transplantation of dissociated WGE cells into the adult brain. To assess FoxP1 expression post-transplantation, E14 mouse WGE cells were transplanted into the lesioned side of the mouse host striatum 10–14 days post-unilateral quinolinic acid-lesion. FoxP1 was expressed within the graft area at the first time point assessed, which was 4 weeks post-transplantation and was still present at 12 weeks, with no significant difference in the numbers of FoxP1 positive cells within the grafts at the two survival times (796 ± 144 and 764 ± 276 respectively; t2 = 0.10, p = n.s; shown for 4 weeks in Fig 5A). We then asked whether FoxP1 expression was also maintained following transplantation of human WGE cells into the quinolinic acid-lesioned rat striatum. Fig 5B shows FoxP1 cells in the graft area at 20 weeks post-transplantation. Calculation of graft volumes revealed 0.4 ± 0.1 mm3 for the mouse-to-mouse transplants, and 13.9 ± 0.9 mm3 for the human-to-rat transplants. These results demonstrate that there is continued expression of FoxP1 post-transplantation as the cells differentiate and integrate into the host striatum, supporting the notion that FoxP1 is a reliable marker of developing and mature MSNs for cell replacement studies. |
View Article: PubMed Central - PubMed
Affiliation: Brain Repair Group, Sir Martin Evans Building, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, United Kingdom.