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.

• Klíčová slova
• DARPP-32, FoxP1, Huntington's disease, Medium spiny neurons, Neural transplantation,
• MeSH
• buněčná diferenciace fyziologie   MeSH
• corpus striatum * cytologie   embryologie   růst a vývoj   MeSH
• dopaminem a cAMP regulovaný fosfoprotein 32 metabolismus   MeSH
• embryo savčí MeSH
• endodeoxyribonukleasy MeSH
• forkhead transkripční faktory genetika   metabolismus   MeSH
• jaderné proteiny metabolismus   MeSH
• kultivované buňky MeSH
• myši knockoutované MeSH
• myši MeSH
• neparametrická statistika MeSH
• nervové kmenové buňky fyziologie   transplantace   MeSH
• neurony cytologie   metabolismus   MeSH
• novorozená zvířata MeSH
• plod cytologie   MeSH
• proteiny nervové tkáně metabolismus   MeSH
• represorové proteiny genetika   metabolismus   MeSH
• techniky in vitro MeSH
• transportní proteiny metabolismus   MeSH
• vývojová regulace genové exprese fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dopaminem a cAMP regulovaný fosfoprotein 32 MeSH
• endodeoxyribonukleasy MeSH
• forkhead transkripční faktory MeSH
• FOXP1 protein, human MeSH Prohlížeč
• jaderné proteiny MeSH
• proteiny nervové tkáně MeSH
• RBBP8 protein, human MeSH Prohlížeč
• represorové proteiny MeSH
• transportní proteiny MeSH