Phenotypic Convergence: Distinct Transcription Factors Regulate Common Terminal Features

Cell. 2018 Jul 26;174(3):622-635.e13. doi: 10.1016/j.cell.2018.05.021. Epub 2018 Jun 18.


Transcription factors regulate the molecular, morphological, and physiological characteristics of neurons and generate their impressive cell-type diversity. To gain insight into the general principles that govern how transcription factors regulate cell-type diversity, we used large-scale single-cell RNA sequencing to characterize the extensive cellular diversity in the Drosophila optic lobes. We sequenced 55,000 single cells and assigned them to 52 clusters. We validated and annotated many clusters using RNA sequencing of FACS-sorted single-cell types and cluster-specific genes. To identify transcription factors responsible for inducing specific terminal differentiation features, we generated a "random forest" model, and we showed that the transcription factors Apterous and Traffic-jam are required in many but not all cholinergic and glutamatergic neurons, respectively. In fact, the same terminal characters often can be regulated by different transcription factors in different cell types, arguing for extensive phenotypic convergence. Our data provide a deep understanding of the developmental and functional specification of a complex brain structure.

Keywords: Drosophila optic lobe; cell-type evolution; gene regulation; modeling; neuronal development; neuronal diversity; neurotransmitters; scRNA-seq; single-cell sequencing; transcription factors.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cholinergic Neurons / physiology
  • Cluster Analysis
  • Computer Simulation
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Developmental / physiology*
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins / metabolism
  • Maf Transcription Factors, Large / metabolism
  • Neurogenesis / physiology*
  • Neuroglia / physiology
  • Neurons / physiology
  • Neurotransmitter Agents / genetics
  • Neurotransmitter Agents / physiology
  • Optic Lobe, Nonmammalian / physiology
  • Phenotype
  • Proto-Oncogene Proteins / metabolism
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology


  • Drosophila Proteins
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Maf Transcription Factors, Large
  • Neurotransmitter Agents
  • Proto-Oncogene Proteins
  • Transcription Factors
  • ap protein, Drosophila
  • tj protein, Drosophila