Segment-Specific Neuronal Subtype Specification by the Integration of Anteroposterior and Temporal Cues

Segment-Specific Neuronal Subtype Specification by the Integration of Anteroposterior and Temporal Cues

Karlsson D, Baumgardt M, Thor S (2010)

PLoS Biol 8(5): e1000368. doi:10.1371/journal.pbio.1000368

Figure 12. Summary of Hox/Pbx/Meis and temporal control of NB 5–6 development

The generation of distinct neuronal subtypes at different axial levels relies upon both anteroposterior and temporal cues. However, the integration between these cues is poorly understood. In the Drosophila central nervous system, the segmentally repeated neuroblast 5–6 generates a unique group of neurons, the Apterous (Ap) cluster, only in thoracic segments. Recent studies have identified elaborate genetic pathways acting to control the generation of these neurons. These insights, combined with novel markers, provide a unique opportunity for addressing how anteroposterior and temporal cues are integrated to generate segment-specific neuronal subtypes. We find that Pbx/Meis, Hox, and temporal genes act in three different ways. Posteriorly, Pbx/Meis and posterior Hox genes block lineage progression within an early temporal window, by triggering cell cycle exit. Because Ap neurons are generated late in the thoracic 5–6 lineage, this prevents generation of Ap cluster cells in the abdomen. Thoracically, Pbx/Meis and anterior Hox genes integrate with late temporal genes to specify Ap clusters, via activation of a specific feed-forward loop. In brain segments, “Ap cluster cells” are present but lack both proper Hox and temporal coding. Only by simultaneously altering Hox and temporal gene activity in all segments can Ap clusters be generated throughout the neuroaxis. This study provides the first detailed analysis, to our knowledge, of an identified neuroblast lineage along the entire neuroaxis, and confirms the concept that lineal homologs of truncal neuroblasts exist throughout the developing brain. We furthermore provide the first insight into how Hox/Pbx/Meis anteroposterior and temporal cues are integrated within a defined lineage, to specify unique neuronal identities only in thoracic segments. This study reveals a surprisingly restricted, yet multifaceted, function of both anteroposterior and temporal cues with respect to lineage control and cell fate specification.

Author Summary
An animal’s nervous system contains a wide variety of neuronal subtypes generated from neural progenitor (“stem”) cells, which generate different types of neurons at different axial positions and time points. Hence, the generation and specification of unique neuronal subtypes is dependent upon the integration of both spatial and temporal cues within distinct stem cells. The nature of this integration is poorly understood. We have addressed this issue in the Drosophila neuroblast 5–6 lineage. This stem cell is generated in all 18 segments of the central nervous system, stretching from the brain down to the abdomen of the fly, but a larger lineage containing a well-defined set of cells—the Apterous (Ap) cluster—is generated only in thoracic segments. We show that segment-specific generation of the Ap cluster neurons is achieved by the integration of the anteroposterior and temporal cues in several different ways. Generation of the Ap neurons in abdominal segments is prevented by anteroposterior cues stopping the cell cycle in the stem cell at an early stage. In brain segments, late-born neurons are generated, but are differently specified due to the presence of different anteroposterior and temporal cues. Finally, in thoracic segments, the temporal and spatial cues integrate on a highly limited set of target genes to specify the Ap cluster neurons.

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