The pivotal role of Drgx in survival, wiring and identity of T4/T5 neurons

The development of Drosophila melanogaster’s T4/T5 motion-sensing neurons has been extensively studied. Despite identifying many genes, important developmental steps remain unknown. This study investigates the Paired-like homeobox transcription factor Dorsal root ganglia homeobox (Drgx) in T4/T5 neuron development. Drgx expression initiates in T4/T5 neuroblasts and persists in mature neurons. Knockdowns using T4/T5-specific drivers yield distinct phenotypes in the optic lobe, including dendrite mistargeting and reduced lobular plate size due to apoptosis in early knockdowns. Late knockdowns exhibit only extensive mistargeting. Therefore, Drgx plays a dual role, initially inhibiting apoptosis and later on establishing T4/T5 neuron identity and circuit formation. Targeted DamID (TaDa) and RNA-sequencing (RNA-seq) identify Drgx target genes involved in apoptosis and neuron projection development. Therefore, Drgx orchestrates vital stages in T4/T5 neuron development, influencing survival, identity, and circuitry and connects to the previously identified transcription factor Sox102F as a target of Drgx.