A complete temporal transcription factor series in the fly visual system

The brain consists of thousands of neuronal types that are generated by stem cells producing different neuronal types as they age. In Drosophila, this temporal patterning is driven by the successive expression of temporal transcription factors (tTFs) . Here we used single-cell mRNA sequencing to ide...

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Bibliographic Details
Published in:	Nature (London) 2022-04, Vol.604 (7905), p.316-322
Main Authors:	Konstantinides, Nikolaos, Holguera, Isabel, Rossi, Anthony M, Escobar, Aristides, Dudragne, Liébaut, Chen, Yen-Chung, Tran, Thinh N, Martínez Jaimes, Azalia M, Özel, Mehmet Neset, Simon, Félix, Shao, Zhiping, Tsankova, Nadejda M, Fullard, John F, Walldorf, Uwe, Roussos, Panos, Desplan, Claude
Format:	Article
Language:	eng
Subjects:	Animals Biochemistry, Molecular Biology Brain Brain research Development Biology Differentiation Drosophila Drosophila melanogaster - cytology Drosophila melanogaster - genetics Drosophila melanogaster - metabolism Drosophila Proteins - genetics Drosophila Proteins - metabolism Fruit flies Gene Expression Regulation, Developmental Gene sequencing Genes Genomics Insects Life Sciences Medulla oblongata Neural Stem Cells - cytology Neural Stem Cells - metabolism Neurobiology Neurons Neurons - cytology Neurons - metabolism Neurons and Cognition Neurotransmitters Optic lobe Optic Lobe, Nonmammalian - cytology RNA-Seq Single-Cell Analysis Stem cells Transcription factors Transcription Factors - metabolism Vision, Ocular Visual flight Visual Perception Visual system
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Summary:	The brain consists of thousands of neuronal types that are generated by stem cells producing different neuronal types as they age. In Drosophila, this temporal patterning is driven by the successive expression of temporal transcription factors (tTFs) . Here we used single-cell mRNA sequencing to identify the complete series of tTFs that specify most Drosophila optic lobe neurons. We verify that tTFs regulate the progression of the series by activating the next tTF(s) and repressing the previous one(s), and also identify more complex mechanisms of regulation. Moreover, we establish the temporal window of origin and birth order of each neuronal type in the medulla and provide evidence that these tTFs are sufficient to explain the generation of all of the neuronal diversity in this brain region. Finally, we describe the first steps of neuronal differentiation and show that these steps are conserved in humans. We find that terminal differentiation genes, such as neurotransmitter-related genes, are present as transcripts, but not as proteins, in immature larval neurons. This comprehensive analysis of a temporal series of tTFs in the optic lobe offers mechanistic insights into how tTF series are regulated, and how they can lead to the generation of a complete set of neurons.
ISSN:	0028-0836 1476-4687