How serially homologous neuroblasts produce different temporal cohorts along the Drosophila larval body axis.

Neural stem cells are highly flexible, generating different neuronal lineages depending on context. In the Drosophila CNS, 30 types of neural stem cells, or neuroblasts, are repeated in each segment as serial homologs, but produce distinct circuits specialized for different body regions. The full in vivo heterogeneity in stem cell development is still poorly understood. This study aimed to uncover the cellular mechanisms behind the development of regionally specialized circuits from serially homologous neuroblasts, focusing on NB3-3 lineages as a model. Using lineage tracing, Notch manipulations, marker analysis, cell death blockade, and circuit tracing, we mapped neurogenesis and circuit assembly for each NB3-3 lineage across all segments. Our results show that serially homologous neuroblasts in certain regions modify proliferation patterns, adding or omitting temporal cohorts, leading to extra neurons for specialized circuits. Four types of temporal cohorts are produced, but one type, which we term a "fundamental" temporal cohort, appears in every region. Neurons from this cohort are further refined post-mitotically, enabling regional circuit specialization. Our study reveals a framework for the heterogeneous development of serially homologous stem cells.