Regulatory Cocktail for Dopaminergic Neurons in a Protovertebrate Identified by Whole-Embryo Single-Cell Transcriptomics

Genes Dev. 2018 Oct 1;32(19-20):1297-1302. doi: 10.1101/gad.317669.118. Epub 2018 Sep 18.

Abstract

The CNS of the protovertebrate Ciona intestinalis contains a single cluster of dopaminergic (DA) neurons, the coronet cells, which have been likened to the hypothalamus of vertebrates. Whole-embryo single-cell RNA sequencing (RNA-seq) assays identified Ptf1a as the most strongly expressed cell-specific transcription factor (TF) in DA/coronet cells. Knockdown of Ptf1a activity results in their loss, while misexpression results in the appearance of supernumerary DA/coronet cells. Photoreceptor cells and ependymal cells are the most susceptible to transformation, and both cell types express high levels of Meis Coexpression of both Ptf1a and Meis caused the wholesale transformation of the entire CNS into DA/coronet cells. We therefore suggest that the reiterative use of functional manipulations and single-cell RNA-seq assays is an effective means for the identification of regulatory cocktails underlying the specification of specific cell identities.

Keywords: Ciona CNS; ascidian; dopamine; neuronal differentiation; single-cell transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Ciona intestinalis / embryology
  • Ciona intestinalis / genetics*
  • Ciona intestinalis / growth & development
  • Ciona intestinalis / metabolism
  • Dopaminergic Neurons / cytology
  • Dopaminergic Neurons / metabolism*
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Single-Cell Analysis
  • Transcription Factors / metabolism

Substances

  • Transcription Factors