Abstract
Spatial and temporal cues are required to specify neuronal diversity, but how these cues are integrated in neural progenitors remains unknown. Drosophila progenitors (neuroblasts) are a good model: they are individually identifiable with relevant spatial and temporal transcription factors known. Here we test whether spatial/temporal factors act independently or sequentially in neuroblasts. We used Targeted DamID to identify genomic binding sites of the Hunchback temporal factor in two neuroblasts (NB5-6 and NB7-4) that make different progeny. Hunchback targets were different in each neuroblast, ruling out the independent specification model. Moreover, each neuroblast had distinct open chromatin domains, which correlated with differential Hb-bound loci in each neuroblast. Importantly, the Gsb/Pax3 spatial factor, expressed in NB5-6 but not NB7-4, had genomic binding sites correlated with open chromatin in NB5-6, but not NB7-4. Our data support a model in which early-acting spatial factors like Gsb establish neuroblast-specific open chromatin domains, leading to neuroblast-specific temporal factor binding and the production of different neurons in each neuroblast lineage.
Highlights
The generation of neuronal diversity in mammals and Drosophila is a multi-step process
To label NB7-4 and its lineage, we used the previously described R19B03AD R18F07DBD splitGal4 line (Lacin and Truman, 2016). We confirmed that this line labels NB7-4 and its lineage from stage 10 until the end of stage 17 (Figure 2E–G’; Figure 2—figure supplement 1B); the only off-target expression is in the adjacent NB5-6 lineage in 6% of hemisegments (n = 1176)
Both NB5-6-Gal4 and NB7-4-Gal4 lines are first expressed after Hb expression in the NB, but during the ‘Hb competence window’ defined by the presence of Distal antenna (Dan) nuclear protein in stage 9–12 neuroblasts (Figure 2C’ and F’) (Kohwi et al, 2013)
Summary
The generation of neuronal diversity in mammals and Drosophila is a multi-step process. The initial step is the production of the neuroectoderm (ventral in Drosophila, dorsal in mammals) that gives rise to neural progenitors In both systems, the neuroectoderm and neural progenitor population acquire regional differences due to the action of Hox genes and spatial patterning genes (Jessell, 2000). Expanding neural diversity requires a second step called temporal patterning, where individual neural progenitors produce a sequence of distinct neurons and glia (Doe, 2017). In both Drosophila and mammals, this process appears to be regulated, in part, by temporal transcription factors (TTFs) that are sequentially expressed within individual neural progenitors (Kohwi and Doe, 2013). A great deal is known about how spatial factors generate regional diversity, and much has recently been learned about temporal patterning mechanisms, virtually nothing is known about how spatial factors and TTFs are integrated to specify distinct neuronal identities in spatially distinct progenitor populations
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