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.neuronal identity | neuropeptide | neuronal plasticity

The Splice Isoforms of the Drosophila Ecdysis Triggering Hormone Receptor Have Developmentally Distinct Roles

“…This conclusion is consistent with a recent report that activation of CCAP-expressing neurons that also express bursicon (and therefore do not include the AN8-9 neurons) is sufficient to induce head eversion (Kim et al 2015). It is possible that the correlational nature of earlier results (Veverytsa and Allan 2012), which were based on the effects of stochastic ablation of subsets of all CCAP-expressing neurons, may have inadvertently suffered from sampling errors that biased the interpretation to the opposite conclusion. In general, our demonstration that only those CCAP-expressing neurons that coexpress ETHRA block ecdysis underscores the ability of the receptor-based mapping approach described here to correctly identify critical nodes in hormonally controlled behavioral circuits.…”

“…The results presented here provide direct evidence that the subset of CCAP-expressing neurons that coexpresses ETHRA is the one required for head eversion. A previous study of a late-differentiating CCAP-expressing neurons concluded that cells in abdominal neuromeres AN8-9 are required for head eversion (Veverytsa and Allan 2012). However, these neurons are not observed to express ETHRA mRNA (Kim et al 2006b), and we were surprised to likewise find them inconsistently represented in the expression patterns of our ETHR MI00949 -and ETHRA MI00949 -Gal4 lines.…”

“…In particular, late-differentiating CCAP-expressing neurons in the posterior segments of the ventral nerve cord (AN5-9) were often missing. These neurons have previously been shown to be required for pupal ecdysis, with the subset in segments AN8-9 specifically implicated in mediating head eversion (Veverytsa and Allan 2012). However, the latter neurons are not among those reported to express ETHRA based on in situ hybridization studies (Kim et al 2006b), and we likewise find that they are mostly absent from the expression patterns of our ETHR Gal4 lines when visualized by a UAS-EYFP reporter alone.…”

Female-biased dimorphism underlies a female-specific role for post-embryonic Ilp7 neurons inDrosophilafertility

“…Post-embryonic Ilp7 neurons innervate the reproductive tracts but are only necessary for female fertility The additional posterior Ilp7 neurons that appear after larval development might be born through post-embryonic neurogenesis in larvae (Truman, 1990), or are perhaps developmentally frozen to express Ilp7 only after metamorphosis (Veverytsa and Allan, 2012). To discriminate between these possibilities, larvae were fed BrdU between mid L3 and pupariation; BrdU incorporation into Ilp7 neurons was examined at adult day A1 (Fig.…”

“…We compared the effects of killing Ilp7 neurons on male and female fertility, using Ilp7-GAL4 to drive the cell death genes UAS-hid and UAS-reaper (Ilp7-KO) (Zhou et al, 1997;Veverytsa and Allan, 2012). To test male fertility, we mated 1-day-old (A1) Ilp7-KO and control males to new groups of virgin control females each day for 5 days.…”