The mechanisms that generate neural diversity during development remains largely unknown. Here, we use scRNA-seq methodology to discover new features of the Drosophila larval CNS across several key developmental timepoints. We identify multiple progenitor subtypes – both stem cell-like neuroblasts and intermediate progenitors – that change gene expression across larval development, and report on new candidate markers for each class of progenitors. We identify a pool of quiescent neuroblasts in newly hatched larvae and show that they are transcriptionally primed to respond to the insulin signaling pathway to exit from quiescence, including relevant pathway components in the adjacent glial signaling cell type. We identify candidate “temporal transcription factors” (TTFs) that are expressed at different times in progenitor lineages. Our work identifies many cell type specific genes that are candidates for functional roles, and generates new insight into the differentiation trajectory of larval neurons.

Stem cells enter and exit quiescence as part of normal developmental programs and to maintain tissue homeostasis in adulthood. While it is clear that stem cell intrinsic and extrinsic cues, local and systemic, regulate quiescence, it remains unclear whether intrinsic and extrinsic cues coordinate to control quiescence and how cue coordination is achieved. Here, we report that Notch signaling coordinates neuroblast intrinsic temporal programs with extrinsic nutrient cues to regulate quiescence in Drosophila. When Notch activity is reduced, quiescence is delayed or altogether bypassed, with some neuroblasts dividing continuously during the embryonic to larval transition. During embryogenesis before quiescence, neuroblasts express Notch and the Notch ligand, Delta. After division, Delta is partitioned to adjacent GMC daughters where it transactivates Notch in neuroblasts. Over time in response to intrinsic temporal cues and increasing numbers of Delta-expressing daughters, neuroblast Notch activity increases leading to cell cycle exit and consequently, attenuation of Notch pathway activity. Quiescent neuroblasts have low to no active Notch, which is required for exit from quiescence in response to nutrient cues. Thus, Notch signaling coordinates proliferation versus quiescence decisions.

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Besides confirming common phenotypes and detecting rare antigen-negative phenotypes, the use of molecular methods in blood donor typing can prompt the identification of new alleles through discrepancy resolution.

The location of the c.1-69C polymorphism in a GATA motif whose disruption is known to result in a Fy null phenotype, together with the perfect correlation between the presence of the FY*A(-69C) allele and the Fy(a-) phenotype support a cause-effect relationship between the two.