title: Temporally tuned neuronal differentiation supports the functional remodeling of a neuronal network in Drosophila.
abstract: During insect metamorphosis, neuronal networks undergo extensive remodeling by restructuring their connectivity and recruiting newborn neurons from postembryonic lineages. The neuronal network that directs the essential behavior, ecdysis, generates a distinct behavioral sequence at each developmental transition. Larval ecdysis replaces the cuticle between larval stages, and pupal ecdysis externalizes and expands the head and appendages to their adult position. However, the network changes that support these differences are unknown. Crustacean cardioactive peptide (CCAP) neurons and the peptide hormones they secrete are critical for ecdysis; their targeted ablation alters larval ecdysis progression and results in a failure of pupal ecdysis. In this study, we demonstrate that the CCAP neuron network is remodeled immediately before pupal ecdysis by the emergence of 12 late CCAP neurons. All 12 are CCAP efferents that exit the central nervous system. Importantly, these late CCAP neurons were found to be entirely sufficient for wild-type pupal ecdysis, even after targeted ablation of all other 42 CCAP neurons. Our evidence indicates that late CCAP neurons are derived from early, likely embryonic, lineages. However, they do not differentiate to express their peptide hormone battery, nor do they project an axon via lateral nerve trunks until pupariation, both of which are believed to be critical for the function of CCAP efferent neurons in ecdysis. Further analysis implicated ecdysone signaling via ecdysone receptors A/B1 and the nuclear receptor ftz-f1 as the differentiation trigger. These results demonstrate the utility of temporally tuned neuronal differentiation as a hard-wired developmental mechanism to remodel a neuronal network to generate a scheduled change in behavior.
authors.affiliation: Department of Cellular and Physiological Sciences,  University of British Columbia, Vancouver, BC,  Canada V6T 1Z3.
authors.forename: Lyubov
authors.initials: L
authors.lastname: Veverytsa
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Allan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology / Q000502:physiology*; D004440:Ecdysone / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology; D018978:Molting / Q000502:physiology; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D011679:Pupa / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D009479:Neuropeptides; C058620:crustacean cardioactive peptide; D004440:Ecdysone