A complete temporal transcription factor series in the fly visual system

Nikolaos Konstantinides (), Isabel Holguera, Anthony M. Rossi, Aristides Escobar, Liébaut Dudragne, Yen-Chung Chen, Thinh N. Tran, Azalia M. Martínez Jaimes, Mehmet Neset Özel, Félix Simon, Zhiping Shao, Nadejda M. Tsankova, John F. Fullard, Uwe Walldorf, Panos Roussos and Claude Desplan ()
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Nikolaos Konstantinides: New York University
Isabel Holguera: New York University
Anthony M. Rossi: New York University
Aristides Escobar: New York University
Liébaut Dudragne: New York University
Yen-Chung Chen: New York University
Thinh N. Tran: New York University
Azalia M. Martínez Jaimes: New York University
Mehmet Neset Özel: New York University
Félix Simon: New York University
Zhiping Shao: Icahn School of Medicine at Mount Sinai, Institute for Genomics and Multiscale Biology
Nadejda M. Tsankova: Icahn School of Medicine at Mount Sinai
John F. Fullard: Icahn School of Medicine at Mount Sinai, Institute for Genomics and Multiscale Biology
Uwe Walldorf: Saarland University
Panos Roussos: Icahn School of Medicine at Mount Sinai, Institute for Genomics and Multiscale Biology
Claude Desplan: New York University

Nature, 2022, vol. 604, issue 7905, 316-322

Abstract: Abstract 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)1–6. 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.

Date: 2022
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DOI: 10.1038/s41586-022-04564-w

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