Vertebrate and invertebrate brains are organized into different areas with distinct neuron subtypes and functions. While we have some insights into the role of region-specific patterning mechanisms, it is not well understood whether alterations in neurogenesis strategies also contribute to circuit diversification.
In the Drosophila visual system, neurons in four ganglia originate from two neuroepithelia, the outer (OPC) and inner (IPC) proliferation centers. Neuroepithelial cells in the medial OPC directly convert into neural stem cell equivalents, the neuroblasts, to generate medulla neurons. One IPC subdomain, the proximal (p)-IPC, is dedicated to generating two neuron populations, distal cells and lobula plate neurons that include the motion-detecting T4 and T5 neurons. By contrast, we observed that the p-IPC produces offspring using a different mode of neurogenesis. p-IPC neuroepithelial cells gradually convert into progenitors that migrate within cell streams and acquire neuroblast properties in a second domain, the distal (d)-IPC. Progenitors emerge by an epithelial-mesenchymal transition-like mechanism that in part depends on the Snail transcription factor Escargot and Decapentaplegic signaling. Furthermore, we found that the proneural bHLH proteins Lethal of scute and Asense differentially control the supply rate and maturation of neuroblasts, respectively. Neuroblasts switch expression from Asense to Atonal, a third proneural protein. Cross-regulatory interactions of the Sox protein Dichaete and the orphan nuclear receptor Tailless are essential for the transition from Asense to Atonal expression, and the generation of distal cells to lobula plate neurons. These factors thus act as switching factors of neuroblast competence. Finally, we provide evidence that the neuroepithelial default-state is IPC-like and that retinal determination gene network members play a central role in conferring neuroepithelial identity to the OPC, including its neurogenesis mode by direct conversion into neuroblasts.
We propose that the novel neurogenesis mode in the p-IPC und the underlying regulatory mechanisms could represent general strategies for setting-up a new proliferative zone to facilitate spatio-temporal matching of neurogenesis and connectivity across ganglia.