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

Authors:
Open Access
Publisher website
Google Scholar
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.
Funding Information
  • National Institutes of Health (NS076542)
  • Japan Society for the Promotion of Science (20681019, 16H04815, 24687008, 16K07433, 16H04724, 20247031, 16H04824, Pre-Strategic Research for Embryonic Science and Technology)
  • Japan Science and Technology Agency (Pre-Strategic Initiatives)
  • University of Tsukuba (National Bio-Resource Project)
  • Ministry of Education, Culture, Sports, Science and Technology

This publication has 40 references indexed in Scilit: