A complete temporal transcription factor series in the fly visual system.

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Stem cells generate diverse neuronal types as they age.
• Temporal patterning in Drosophila optic lobes is driven by sequential temporal transcription factors (tTFs).

Purpose of the Study:

• To identify the complete series of tTFs specifying Drosophila optic lobe neurons.
• To understand the regulatory mechanisms of tTF series and their role in neuronal diversity.
• To investigate conserved early neuronal differentiation steps in humans.

Main Methods:

• Single-cell mRNA sequencing to identify tTFs.
• Experimental verification of tTF regulatory roles.
• Analysis of neuronal differentiation markers.

Main Results:

• A complete series of tTFs for Drosophila optic lobe neurons was identified.
• tTFs regulate series progression via activation and repression, with complex regulatory mechanisms identified.
• Temporal windows of origin and birth order for medulla neurons were established.
• tTFs sufficiently explain neuronal diversity in the optic lobe.
• Early neuronal differentiation steps, including transcript presence before protein, are conserved in humans.

Conclusions:

• The identified tTF series provides a framework for understanding neuronal diversity generation in the optic lobe.
• tTF regulation is complex, involving sequential activation and repression.
• Conserved early differentiation mechanisms highlight fundamental principles of neurodevelopment across species.