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

ABSTRACT: To understand the developing striatum, key genes during development were identified using microarray analsyis tha could be considered as marker of medium spiny neurons. The ages studied is at peak striatal neurogenesis. 3 different gestational ages of CD1 mice were used with triplicate repeats

ORGANISM(S): Mus musculus

SUBMITTER: Anne Rosser

PROVIDER: E-GEOD-55497 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Project description:To understand the developing striatum, key genes during development were identified using microarray analsyis tha could be considered as marker of medium spiny neurons. The ages studied is at peak striatal neurogenesis.

2016-06-23 | GSE55497 | GEO

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

Project description: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.

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Foxp1 regulates the development of glutamatergic synaptic input onto spiny projection neurons expressing Drd2 [snRNA-seq]

Project description:Long-range glutamatergic inputs from the cortex and thalamus provide important motor and cognitive information to the striatum where they are integrated for learning and action planning. Genetic programs and transcription factors that orchestrate the development of these inputs are relatively unknown. The transcription factor, FOXP1, is crucial for the development of spiny projection neurons (SPNs) in the striatum. We investigated the cell-specific role of Foxp1 in the formation of glutamatergic inputs – including corticostriatal inputs. Embryonic Foxp1 deletion in dopamine receptor 2-expressing SPNs (D2 Foxp1cKO) leads to reduced transmission of corticostriatal excitatory inputs and decreased synaptically driven excitability. Postnatal deletion of Foxp1 also resulted in decreased glutamatergic inputs onto D2 SPNs. Single nuclei RNA sequencing of D2 Foxp1cKO striatum identified downregulated postsynaptic genes, consistent with the synaptic phenotype. Reinstating Foxp1 postnatally rescued electrophysiological deficits and expression of a subset of genes that were altered by embryonic deletion in D2 SPNs. Postnatal Foxp1 reinstatement could also rescue behavioral phenotypes. In summary, we demonstrate that FOXP1 regulates the development of corticostriatal circuitry. Further, changes at multiple levels of brain function resulting from loss of Foxp1 are rescued with postnatal Foxp1 reinstatement, indicating a therapeutic approach for individuals with FOXP1 syndrome.

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RNAseq of FACS Drd1 and Drd2 receptor expressing medium spiny neurons (direct and indirect medium spiny neurons) from 5-6 month Q175 Huntington's disease model mice, compared to WT littermates.

Project description:mRNAseq for baseline transcriptional profiling of D1 and D2 receptor-expressing medium spiny neurons from 5-6 month Q175 mice compared to WT littermates.

2018-09-01 | GSE103345 | GEO

Comparative analysis of Drd1+ Medium Spiny Neurons and Drd2+ Medium Spiny Neurons

Project description:The cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations. Using Bacterial Artificial Chromosome (BAC) transgenic mice which express EGFP-tagged ribosomal protein L10a in defined cell populations, we have developed a methodology to affinity purify polysomal mRNAs from genetically defined cell populations in the brain. The utility of this approach is illustrated by the comparative analysis of four types of neurons, revealing hundreds of genes that distinguish these four cell populations. We find that even two morphologically indistinguishable, intermixed subclasses of medium spiny neuron display vastly different translational profiles and present examples of the physiological significance of such differences. This genetically targeted Translating Ribosome Affinity Purification (TRAP) methodology is a generalizable method useful for the identification of molecular changes in any genetically defined cell type in response to genetic alterations, disease, or pharmacological perturbations. Keywords: Cell Type Comparison For each cell population, D1 and D2, three independent TRAP replicates were collected, and total RNA from the immunoprecipitates were amplified and hybridized. Data were normalized with the GC-RMA algorithm, and expression values on each chip were normalized to that chip’s 50th percentile. Data were then converted to log2 scale. We recommend that only genes where more than one sample has a normalized intensity larger than 16 (4 in log2 scale) should be kept in the analysis.

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Comparative analysis of Drd1+ Medium Spiny Neurons, Drd2+ Medium Spiny Neurons, cocaine treatment

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Tail fan tissue of spiny lobster

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Comparative analysis of Drd1+ Medium Spiny Neurons and Drd2+ Medium Spiny Neurons

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