Phenotypic Convergence: Distinct Transcription Factors Regulate Common Terminal Features

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.

Coordination between stochastic and deterministic specification in the Drosophila visual system

“…Taken together, our data indicate that Dpr11 and DIPγ mediate the pairing of yDm8s with their presynaptic partners yR7s. It is noteworthy that we did not find any other DIPs expressed in pDm8s or pR7s, whereas Dm8s express multiple dprs based on RNAseq data (Konstantinides et al, 2018). This suggests that the matching between pR7 and pDm8s uses cell adhesion molecules distinct from Dprs and DIPs.…”

“…This is achieved through induction of the pR8 fate by pR7s through Activin and BMP signaling while the yR8 fate is specified by default (Mikeladze-Dvali et al, 2005;Wells et al, 2017). R7 and R8 send their axons to the medulla, the second neuropile of the optic lobe where they make synapses with some of the ∼40,000 neurons of more than 80 different cell types that compose the medulla ( Figure 1C) (Fischbach and Dittrich, 1989;Konstantinides et al, 2018). The medulla is retinotopically organized in ∼750 columns that correspond to the ∼750 ommatidia as medulla neurons preserve their spatial relationship to the retina.…”

FMRP binding to a ranked subset of long genes is revealed by coupled CLIP and TRAP in specific neuronal cell types

“…Recent experiments using labeled cell sorting 68 and single cell RNA sequencing [69][70][71][72][73] have revealed great heterogeneity in gene expression among the cells of the CNS. This is true at the level of characteristic patterns that define different cell populations as well as different responses among these cells to input or disease processes 74 .…”

The astrocyte-enriched geneCG11000plays a crucial role in the development, locomotion and lifespan ofD. melanogaster

“…In this study, the transcriptome of 55,000 single cells within the optic lobe of D. melanogaster brain was analyzed to identify novel cell type-specific genes followed by functional analysis of the genes. The optic lobe occupies about two-third of whole D. melanogaster brain [19] with diverse set of cells including the above-mentioned cell types [12].…”