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

Identifying the steps involved in striatal development is important both for understanding the striatum in health and disease, and for generating protocols to differentiate striatal neurons for regenerative medicine. The most prominent neuronal subtype in the adult striatum is the medium spiny projection neuron (MSN), which constitutes more than 85% of all striatal neurons and classically expresses DARPP-32. Through a microarray study of genes expressed in the whole ganglionic eminence (WGE: the developing striatum) in the mouse, we identified the gene encoding the transcription factor Forkhead box protein P1 (FoxP1) as the most highly up-regulated gene, thus providing unbiased evidence for the association of FoxP1 with MSN development. We also describe the expression of FoxP1 in the human fetal brain over equivalent gestational stages. FoxP1 expression persisted through into adulthood in the mouse brain, where it co-localised with all striatal DARPP-32 positive projection neurons and a small population of DARPP-32 negative cells. There was no co-localisation of FoxP1 with any interneuron markers. FoxP1 was detectable in primary fetal striatal cells following dissection, culture, and transplantation into the adult lesioned striatum, demonstrating its utility as an MSN marker for transplantation studies. Furthermore, DARPP-32 expression was absent from FoxP1 knock-out mouse WGE differentiated in vitro, suggesting that FoxP1 is important for the development of DARPP-32-positive MSNs. 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.

Differential effects of unilateral striatal and nigrostriatal lesions on grip strength, skilled paw reaching and drug-induced rotation in the rat.

Lateralised motor deficits associated with basal ganglia dysfunction were compared in separate groups of rats receiving unilateral 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal pathway, quinolinic acid-induced lesions of the striatum, or sham control injections. Amphetamine induced ipsilateral rotation in both lesion groups, whereas a low ('supersensitive') dose of apomorphine induced rotation only in the nigrostriatal lesion group. Both lesions induced impairments in skilled paw reaching with the contralateral paw in the 'staircase' test; by contrast the striatal lesions also induced a marked impairment with the ipsilateral paw, which was unaffected by the nigrostriatal lesion. A previously reported increase in grip strength with the contralateral paw after nigrostriatal lesion was replicated, whereas striatal lesions induced only minor bilateral deficits in this test. The results are discussed in the context of the utility, reliability and validity of alternative tests of motor deficit in animal models of Parkinson's and Huntington's diseases.