Dataset Information

Neuronal diversity and convergence in a visual system developmental atlas (bulk RNA-seq)

ABSTRACT: Deciphering how neuronal diversity is established and maintained requires a detailed knowledge of neuronal gene expression throughout development. In contrast to mammalian brains, the large neuronal diversity of the Drosophila optic lobes and its connectome are almost completely characterized. However, a molecular characterization of this diversity, particularly during development, has been lacking. We present novel insights into brain development through a nearly exhaustive description of the transcriptomic diversity of the optic lobes. We acquired the transcriptome of 275,000 single-cells at adult and five pupal stages, and developed a machine learning framework to assign them to almost 200 cell-types at all timepoints. We discovered two large neuronal populations that wrap neuropils during development but die just before adulthood, as well as neuronal subtypes that partition dorsal and ventral visual circuits by differential Wnt signaling throughout development. Moreover, we showed that neurons of the same type but produced days apart synchronize their transcriptomes shortly after being produced. We also resolved during synaptogenesis neuronal subtypes that converge to indistinguishable transcriptomic profiles in adults while greatly differing in morphology and connectivity. Our datasets almost completely account for the known neuronal diversity of the optic lobes and serve as a paradigm to understand brain development across species.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE142788 | GEO | 2020/07/16

REPOSITORIES: GEO

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Project description:One of the key regulatory mechanisms of brain size and neuronal diversity is through control of NB identity via cell fate maintenance. Dedifferentiation is the reversion of differentiated cells to a stem cell like fate, whereby, the gene expression program of mature cells is altered and genes associated with multipotency are expressed. Beyond the fact that misexpression of these factors and pathways caused the formation of ectopic NBs, whether these dedifferentiated NBs faithfully produce the correct number and types of neurons or glial cells, or undergo timely terminal differentiation, has not been assessed. These characteristics are key determinants of overall CNS size and function, thus are important parameters when considering whether dedifferentiation leads to tumourigenesis or can be appropriately utilized for regenerative purposes. Appropriate terminal differentiation as well as neuronal diversity are key characteristics of NSCs, and are specified through temporal patterning of the NSCs driven by the successive expression of temporal transcription factors (tTFs). In this study, we found that ectopic NSCs induced via bHLH transcription factor Deadpan (Dpn) expression in the optic lobes of the developing Drosophila CNS fail to undergo appropriate temporal progression, where they express mid-tTF, Sloppy-paired 1 (Slp-1) at the expense of late-tTF Tailless (Tll); consequently generating an excess of Twin of eyeless (Toy) positive neurons and fewer Reversed polarity (Repo) positive glial cells. Dpn overexpression also resulted in stalled progression through the cell cycle, and a failure to undergo timely terminal differentiation. Mechanistically, DamID studies demonstrated that Dpn directly binds to both Dichaete (D), a Sox-box transcription factor known to repress Slp-1, as well as a number of cell cycle genes. Promoting cell cycle progression or overexpression of D were able to re-trigger the progression of the temporal series in dedifferentiated NBs, restoring both neuronal diversity and timely NB terminal differentiation.

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Neuronal diversity and convergence in a visual system developmental atlas (bulk RNA-seq)

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