Neuronal identities derived by misexpression of the POU IV sensory determinant in a protovertebrate

Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2118817119. doi: 10.1073/pnas.2118817119.

Abstract

The protovertebrate Ciona intestinalis type A (sometimes called Ciona robusta) contains a series of sensory cell types distributed across the head-tail axis of swimming tadpoles. They arise from lateral regions of the neural plate that exhibit properties of vertebrate placodes and neural crest. The sensory determinant POU IV/Brn3 is known to work in concert with regional determinants, such as Foxg and Neurogenin, to produce palp sensory cells (PSCs) and bipolar tail neurons (BTNs), in head and tail regions, respectively. A combination of single-cell RNA-sequencing (scRNA-seq) assays, computational analysis, and experimental manipulations suggests that misexpression of POU IV results in variable transformations of epidermal cells into hybrid sensory cell types, including those exhibiting properties of both PSCs and BTNs. Hybrid properties are due to coexpression of Foxg and Neurogenin that is triggered by an unexpected POU IV feedback loop. Hybrid cells were also found to express a synthetic gene battery that is not coexpressed in any known cell type. We discuss these results with respect to the opportunities and challenges of reprogramming cell types through the targeted misexpression of cellular determinants.

Keywords: cell-type specification; cellular reprogramming; computational biology; evolutionary developmental biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution
  • Cellular Reprogramming / genetics
  • Cellular Reprogramming / physiology
  • Ciona intestinalis / genetics*
  • Ciona intestinalis / metabolism
  • Epidermis / innervation
  • Epidermis / metabolism
  • Gene Expression / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Gene Regulatory Networks / genetics
  • Neural Crest / metabolism
  • Neural Plate / metabolism
  • Neurons / metabolism*
  • POU Domain Factors / genetics
  • POU Domain Factors / metabolism*
  • Single-Cell Analysis
  • Transcription Factors / metabolism
  • Vertebrates / genetics

Substances

  • POU Domain Factors
  • Transcription Factors