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FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation.

Precious SV, Kelly CM, Reddington AE, Vinh NN, Stickland RC, Pekarik V, Scherf C, Jeyasingham R, Glasbey J, Holeiter M, Jones L, Taylor MV, Rosser AE - Exp. Neurol. (2016)

Bottom Line: 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.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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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.


FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation.

Precious SV, Kelly CM, Reddington AE, Vinh NN, Stickland RC, Pekarik V, Scherf C, Jeyasingham R, Glasbey J, Holeiter M, Jones L, Taylor MV, Rosser AE - Exp. Neurol. (2016)

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.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4920670&req=5

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.

Bottom Line: 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.

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.

No MeSH data available.


Related in: MedlinePlus