The molecular landscape of neural differentiation in the developing Drosophila brain revealed by targeted scRNA-seq and multi-informatic analysis

The Drosophila type II neuroblast lineages present an attractive model to investigate the neurogenesis and differentiation process as they adapt to a process similar to that in the human outer subventricular zone. We perform targeted single-cell mRNA sequencing in third instar larval brains to study this process of the type II NB lineage. Combining prior knowledge, in silico analyses, and in situ validation, our multi-informatic investigation describes the molecular landscape from a single developmental snapshot. 17 markers are identified to differentiate distinct maturation stages. 30 markers are identified to specify the stem cell origin and/or cell division numbers of INPs, and at least 12 neuronal subtypes are identified. To foster future discoveries, we provide annotated tables of pairwise gene-gene correlation in single cells and MiCV, a web tool for interactively analyzing scRNA-seq datasets. Taken together, these resources advance our understanding of the neural differentiation process at the molecular level. [Display omitted] •4,035 type II cells from developing Drosophila brains are profiled using scRNA-seq•Pseudotime analysis reveals genes that vary during neural differentiation•Identified marker genes specify INPs in age- and lineage-restricted fashions•Transcription factors and surface molecules mark developing neural progenies Using a combination of targeted scRNA-seq, in situ RNA staining, and a multi-informatic analysis paradigm, Michki et al. characterize the transcriptome landscape of thousands of type II neurons and their progenitors in the developing larval fruit fly brain.