Transcription factor codes patterning neuronal groundplans of the cerebrum

Brain regions that regulate motivated behaviours, including the vertebrate hypothalamus and arthropod cerebrum, house bespoke neural circuits dedicated to perceptual and internal regulation of many behavioural states1,2. These circuits are built to purpose from complex sets of cell types whose patterning has been challenging to elucidate. Here we developed methods in Drosophila melanogaster to embed well-studied neurons that regulate mating in the transcriptional contexts of the neuronal lineages that generate them3–5. By comparing transcription within and between lineages, we identified a large set of transcription factors expressed in complex combinations that delineate cerebral hemilineages—classes of postmitotic neurons born from the same stem cell and sharing Notch status6,7. Hemilineages comprise the major anatomic classes in the cerebrum8–10 and these transcription factors are required to generate their gross features. We show that subtypes of the same hemilineage can provide a common computational module to circuits regulating different drives, and identify an orthogonal set of transcription factors that stratify hemilineage subtypes of differing birth order. Our findings suggest that distinct sets of transcription factors operate in a hierarchical system to build, diversify and sexually differentiate lineally related neurons that compose motivated behaviour circuits. By linking developmental patterning to separable transcriptional axes that produce gross versus fine aspects of information flow, we provide a logical framework for cerebral control of diverse drives. Researchers mapped how transcription factors define neuron lineages in fruit fly brains, revealing hierarchical genetic programs that shape and specialize circuits controlling motivated behaviours such as mating.