Female Aedes aegypti mosquitoes are deadly vectors of arboviral pathogens and breed in containers of freshwater associated with human habitation. Because high salinity is lethal to offspring, correctly evaluating water purity is a crucial parenting decision. We found that the DEG/ENaC channel ppk301 and sensory neurons expressing ppk301 control egg-laying initiation and choice in Ae. aegypti. Using calcium imaging, we found that ppk301-expressing cells show ppk301-dependent responses to water but, unexpectedly, also respond to salt in a ppk301-independent fashion. This suggests that ppk301 is instructive for egg-laying at low salt concentrations, but that a ppk301-independent pathway is responsible for inhibiting egg-laying at high salt concentrations. Water is a key resource for insect survival and understanding how mosquitoes interact with water to control different behaviors is an opportunity to study the evolution of chemosensory systems.
Source data for all plots in Figures 1-3 and Figure 5-7 are provided in Supplementary File 1.
The neurotranscriptome of the Aedes aegypti mosquito.NCBI BioProject, PRJNA236239.
| Improved reference genome of Aedes aegypti informs arbovirus vector control.NCBI Assembly, GCF_002204515.2.
- Benjamin J Matthews
- Leslie B Vosshall
- Benjamin J Matthews
- Meg A Younger
- Meg A Younger
- Meg A Younger
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: For routine strain maintenance, animals were blood-fed on live mice or human subjects. Adult females of all genotypes were blood-fed on a single human subject during mutant generation, for behavioral assays, and calcium imaging. Blood-feeding procedures with live hosts were approved and monitored by The Rockefeller University Institutional Animal Care and Use Committee (IACUC protocol 15772) and Institutional Review Board, (IRB protocol LV-0652). Human subjects gave their written informed consent to participate.
Human subjects: For routine strain maintenance, animals were blood-fed on live mice or human subjects. Adult females of all genotypes were blood-fed on a single human subject during mutant generation, for behavioral assays, and calcium imaging. Blood-feeding procedures with live hosts were approved and monitored by The Rockefeller University Institutional Animal Care and Use Committee (IACUC protocol 15772) and Institutional Review Board, (IRB protocol LV-0652). Human subjects gave their written informed consent to participate.
- Kristin Scott, University of California, Berkeley, United States
© 2019, Matthews et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
The heteroplasmic state of eukaryotic cells allows for cryptic accumulation of defective mitochondrial genomes (mtDNA). ‘Purifying selection’ mechanisms operate to remove such dysfunctional mtDNAs. We found that activators of programmed cell death (PCD), including the CED-3 and CSP-1 caspases, the BH3-only protein CED-13, and PCD corpse engulfment factors, are required in C. elegans to attenuate germline abundance of a 3.1-kb mtDNA deletion mutation, uaDf5, which is normally stably maintained in heteroplasmy with wildtype mtDNA. In contrast, removal of CED-4/Apaf1 or a mutation in the CED-4-interacting prodomain of CED-3, do not increase accumulation of the defective mtDNA, suggesting induction of a non-canonical germline PCD mechanism or non-apoptotic action of the CED-13/caspase axis. We also found that the abundance of germline mtDNAuaDf5 reproducibly increases with age of the mothers. This effect is transmitted to the offspring of mothers, with only partial intergenerational removal of the defective mtDNA. In mutants with elevated mtDNAuaDf5 levels, this removal is enhanced in older mothers, suggesting an age-dependent mechanism of mtDNA quality control. Indeed, we found that both steady-state and age-dependent accumulation rates of uaDf5 are markedly decreased in long-lived, and increased in short-lived, mutants. These findings reveal that regulators of both PCD and the aging program are required for germline mtDNA quality control and its intergenerational transmission.
A hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A hallmark of ALS/FTD pathology is the presence of dipeptide repeat (DPR) proteins, produced from both sense GGGGCC (poly-GA, poly-GP, poly-GR) and antisense CCCCGG (poly-PR, poly-PG, poly-PA) transcripts. Translation of sense DPRs, such as poly-GA and poly-GR, depends on non-canonical (non-AUG) initiation codons. Here, we provide evidence for canonical AUG-dependent translation of two antisense DPRs, poly-PR and poly-PG. A single AUG is required for synthesis of poly-PR, one of the most toxic DPRs. Unexpectedly, we found redundancy between three AUG codons necessary for poly-PG translation. Further, the eukaryotic translation initiation factor 2D (EIF2D), which was previously implicated in sense DPR synthesis, is not required for AUG-dependent poly-PR or poly-PG translation, suggesting that distinct translation initiation factors control DPR synthesis from sense and antisense transcripts. Our findings on DPR synthesis from the C9ORF72 locus may be broadly applicable to many other nucleotide repeat expansion disorders.