A complete temporal transcription factor series in the fly visual system

Nikolaos Konstantinides (1, 2) , Isabel Holguera (2) , Anthony Rossi (2) , Aristides Escobar (2) , Liébaut Dudragne (2) , Yen-Chung Chen (2) , Thinh Tran (2) , Azalia Martínez Jaimes (2) , Mehmet Neset Özel (2) , Félix Simon (2) , Zhiping Shao , Nadejda Tsankova , John Fullard , Uwe Walldorf , Panos Roussos , Claude Desplan (2, 3)

1 IJM (UMR_7592) - Institut Jacques Monod
2 Department of Biology [New York]
3 New York University [Abu Dhabi]

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.

Domaines: Biologie du développement; Neurobiologie; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Nikolaos Konstantinides, Isabel Holguera, Anthony Rossi, Aristides Escobar, Liébaut Dudragne, et al.. A complete temporal transcription factor series in the fly visual system. Nature, 2022, 604 (7905), pp.316-322. ⟨10.1038/s41586-022-04564-w⟩. ⟨hal-03663877⟩