title: Segment-specific neuronal subtype specification by the integration of anteroposterior and temporal cues.
abstract: 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Karlsson
authors.forename: Magnus
authors.initials: M
authors.lastname: Baumgardt
authors.forename: Stefan
authors.initials: S
authors.lastname: Thor
mesh_terms: D000005:Abdomen / Q000502:physiology; D000818:Animals; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation; D002490:Central Nervous System / Q000166:cytology*; D004330:Drosophila / Q000166:cytology* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013909:Thorax / Q000166:cytology
chemical_list: D029721:Drosophila Proteins