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bioRxiv · 10.1101/611780

Single-cell analysis of Foxp1-driven mechanisms essential for striatal development

Anderson, A. G.·Kulkarni, A.·Harper, M.·Konopka, G.
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Abstract

The striatum is a critical forebrain structure for integrating cognitive, sensory, and motor information from diverse brain regions into meaningful behavioral output. However, the transcriptional mechanisms that underlie striatal development and organization at single-cell resolution remain unknown. Here, we show that Foxp1, a transcription factor strongly linked to autism and intellectual disability, regulates organizational features of striatal circuitry in a cell-type-dependent fashion. Using single-cell RNA-sequencing, we examine the cellular diversity of the early postnatal striatum and find that cell-type-specific deletion of Foxp1 in striatal projection neurons alters the cellular composition and neurochemical architecture of the striatum. Importantly, using this approach, we identify the non-cell autonomous effects produced by disrupting Foxp1 in one cell-type and the molecular compensation that occurs in other populations. Finally, we 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. These data reveal cell-type-specific transcriptional mechanisms underlying distinct features of striatal circuitry and identify Foxp1 as a key regulator of striatal development.

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Anderson, A. G., Kulkarni, A., Harper, M., Konopka, G.. 2019-04-18. Single-cell analysis of Foxp1-driven mechanisms essential for striatal development. https://doi.org/10.1101/611780

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