Variations at a quantitative trait locus (QTL) affect development of behavior in lead-exposed Drosophila melanogaster

Abstract

We developed Drosophila melanogaster as a model to study correlated behavioral, neuronal and genetic effects of the neurotoxin lead, known to affect cognitive and behavioral development in children. We showed that, as in vertebrates, lead affects both synaptic development and complex behaviors (courtship, fecundity, locomotor activity) in Drosophila. By assessing differential behavioral responses to developmental lead exposure among recombinant inbred Drosophila lines (RI), derived from parental lines Oregon R and Russian 2b, we have now identified a genotype by environment interaction (GEI) for a behavioral trait affected by lead. Drosophila Activity Monitors (TriKinetics, Waltham, MA), which measure activity by counting the number of times a single fly in a small glass tube walks through an infrared beam aimed at the middle of the tube, were used to measure activity of flies, reared from eggs to 4 days of adult age on either control or lead-contaminated medium, from each of 75 RI lines. We observed a significant statistical association between the effect of lead on average daytime activity across lines and one marker locus, 30AB, on chromosome 2; we define this as a Quantitative Trait Locus (QTL) associated with behavioral effects of developmental lead exposure. When 30AB was from Russian 2b, lead significantly increased locomotor activity, whereas, when 30AB was from Oregon R, lead decreased it. 30AB contains about 125 genes among which are likely “candidate genes” for the observed lead-dependent behavioral changes. Drosophila are thus a useful, underutilized model for studying behavioral, synaptic and genetic changes following chronic exposure to lead or other neurotoxins during development.

Accumulation, elimination, sequestration, and genetic variation of lead (Pb2+) loads within and between generations of Drosophila melanogaster

“…These lines vary in the presence or absence of site-specific DNA markers at approximately 80 sites throughout the genome. Flies were reared as described in Hirsch et al (2009) in either control or leaded medium (250 μM PbAc). Flies were tested for Pb load at six d post-eclosion.…”

“…Several measurable endpoints have been suggested by others for the use of Drosophila as a toxicology model (Rand, 2010; Rand et al, 2014); these include, but are not limited to, lethality, morphology, behavioral traits, embryonic development, and targeted mechanistic studies. We have established D. melanogaster as a model system to investigate the behavioral, physiological, and genetic effects of chronic, developmental Pb exposure (He et al, 2009; Hirsch et al, 2003; Hirsch et al, 2009; Morley et al, 2003; Ruden et al, 2009). …”

“…Previous studies have found that D. melanogaster readily accumulates Pb (Cohn et al, 1992; Hirsch et al, 2003), and that Pb is toxic for both larvae (Akins et al, 1992) and adults (Hirsch et al, 2003). In previous research, we identified a region of the Drosophila genome that is involved in Pb-dependent changes in locomotor activity (Hirsch et al, 2009) and in extensive changes in patterns of transcription induced by developmental Pb exposure (Ruden et al, 2009). …”

Genetic aspects of behavioral neurotoxicology

“…30AB contains about 125 genes among which are likely “candidate genes” for the observed lead-dependent behavioral changes. To the best of our knowledge, this is the first identification of a portion of the D. melanogaster genome that is involved in a behavioral response to lead (Hirsch et al, 2009). Using D. melanogaster , we have identified a “critical period” (the first 4 days of adult life) during which lead affects adult behaviors.…”

Food searching behaviour of a Lepidoptera pest species is modulated by the foraging gene polymorphism

“…The 'actimeter' system for automated recording of larval foraging activity This system was designed by Chardonnet et al (Chardonnet et al, 2012) from a device initially developed for the fruit fly, the DAM system (Drosophila Activity Monitoring System, DAM2 ® ; Trikinetics, Waltham, MA, USA) (Freeman et al, 2010;Hirsch et al, 2009;Huang et al, 2009). The actimeter apparatus is made of tubular units (200×7 mm i.d.…”