Phenotypic Convergence: Distinct Transcription Factors Regulate Common Terminal Features

Nikolaos Konstantinides, Katarina Kapuralin, Chaimaa Fadil, Luendreo Barboza, Rahul Satija, Claude Desplan

Research output: Contribution to journalArticle

Abstract

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. A single-cell analysis of the fly optic lobe reveals extensive phenotypic convergence with different sets of transcription factors, promoting similar outcomes in different cell types.

Original languageEnglish (US)
Pages (from-to)622-635.e13
JournalCell
Volume174
Issue number3
DOIs
StatePublished - Jul 26 2018

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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