Single-Cell Analysis of Foxp1-Driven Mechanisms Essential for Striatal Development.

The striatum is a critical forebrain structure integrating cognitive, sensory, and motor information from diverse brain regions into meaningful behavioral output. However, the transcriptional mechanisms underlying striatal development at single-cell resolution remain unknown. Using single-cell RNA sequencing (RNA-seq), we examine the cellular diversity of the early postnatal striatum and show that Foxp1, a transcription factor strongly linked to autism and intellectual disability, regulates the cellular composition, neurochemical architecture, and connectivity of the striatum in a cell-type-dependent fashion. We also identify Foxp1-regulated target genes within distinct cell types and connect these molecular changes to functional and behavioral deficits relevant to phenotypes described in patients with FOXP1 loss-of-function mutations. Using this approach, we could also examine the non-cell-autonomous effects produced by disrupting one cell type and the molecular compensation that occurs in other populations. These data reveal the cell-type-specific transcriptional mechanisms regulated by Foxp1 that underlie distinct features of striatal circuitry. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Ashley G Anderson, Ashwinikumar Kulkarni, Matthew Harper, Genevieve Konopka. Single-Cell Analysis of Foxp1-Driven Mechanisms Essential for Striatal Development. Cell reports. 2020 Mar 03;30(9):3051-3066.e7

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PMID: 32130906

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