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

Genes & Development
Takeo HorieMichael Levine

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.

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Citations

Apr 16, 2020·Marine Drugs·Valeria LongoPaolo Colombo
Oct 23, 2019·Developmental Biology·Susanne GibboneyAlberto Stolfi
Apr 30, 2021·Science Advances·Laurence A LemaireMichael Levine
Nov 6, 2018·Developmental Biology·Sarthak SharmaAlberto Stolfi
Jan 22, 2019·Developmental Biology·Alicia MadgwickPatrick Lemaire
Sep 2, 2021·BMC Biology·Konner M WinkleyMichael T Veeman
Sep 2, 2021·Annual Review of Biomedical Data Science·Angela Oliveira PiscoAaron McGeever
Dec 11, 2021·Science Advances·Taichi AkahoshiKohji Hotta

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