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

Cell Rep. 2020 Mar 3;30(9):3051-3066.e7. doi: 10.1016/j.celrep.2020.02.030.


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.

Keywords: FOXP1; autism; neurodevelopment; single-cell RNA sequencing; striatum.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Corpus Striatum / growth & development*
  • Corpus Striatum / metabolism*
  • Forkhead Transcription Factors / deficiency
  • Forkhead Transcription Factors / metabolism*
  • Gene Deletion
  • Globus Pallidus / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / metabolism
  • Repressor Proteins / deficiency
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Single-Cell Analysis*
  • Up-Regulation


  • Biomarkers
  • Forkhead Transcription Factors
  • Foxp1 protein, mouse
  • Repressor Proteins