Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics

Takeo Horie, Ryoko Horie, Kai Chen, Chen Cao, Masashi Nakagawa, Takehiro G. Kusakabe, Noriyuki Satoh, Yasunori Sasakura, Michael Levine

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1297-1302
Number of pages6
JournalGenes and Development
Volume32
Issue number19-20
DOIs
StatePublished - 2018

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Keywords

  • Ascidian
  • Ciona CNS
  • Dopamine
  • Neuronal differentiation
  • Single-cell transcriptomics

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    Horie, T., Horie, R., Chen, K., Cao, C., Nakagawa, M., Kusakabe, T. G., Satoh, N., Sasakura, Y., & Levine, M. (2018). Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics. Genes and Development, 32(19-20), 1297-1302. https://doi.org/10.1101/GAD.317669.118