Event:

In the Drosophila optic lobes, more than 250 types of neurons organized as 800 columns process the inputs from 800 unit-eyes. We study how this variety of neurons is generated during development and how connectivity among these neurons is regulated.
The neural stem cells in the medulla sequentially express a series of temporal transcription factors (tTFs), producing at each temporal window different neurons that innervate each of the 800 columns. At each division, the neural stem cell produces an intermediate precursor that divides once, generating a NotchON and a NotchOFF neuron.
We used single-cell mRNA sequencing to identify the complete series of tTFs that specify most optic lobe neurons from birth to adulthood. Each tTF regulates the progression of the series by activating the next tTF and repressing the previous one. This allowed us to establish the temporal window of origin and birth order of each neuronal type in the medulla. These tTFs are sufficient to explain the generation of the entire neuronal diversity in this brain region by integrating temporal and spatial patterning as well as their Notch status.
However, because the cell cycle is slower than the transitions between temporal windows and the two are not synchronized, not all neuroblasts ’use’ all temporal windows and thus only produce a stochastic subset of the total neural types that can be specified by this neuroblast, thus providing flexibility to the system.
We also discovered that the ~250 ’distinct neurons’ in the Drosophila visual system can be defined by unique combinations of 10 terminal selector TFs that are continuously expressed in each neuron from birth to adulthood. Targeted modifications of this ’selector’ code induce predictable conversions of cell fates between neurons that appear to be morphologically and transcriptionally complete. Using single nuclei ATAC-seq data, we showed that Cis-regulatory sequences link this ’selector’ program to the upstream tTFs that specify neuronal fates. This provides a generalizable framework of how specific fates are initiated and maintained in postmitotic neurons.