Steroid Receptor Isoform Expression in Drosophila Nociceptor Neurons Is Required for Normal Dendritic Arbor and Sensitivity.
Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in the primary nociceptor neurons, known as the class IV multidendritic neurons. Suppression of EcRA by RNA interference in these cells leads to hyposensitivity to noxious stimulation. Suppression of EcRB1 leads to reduction of dendritic branching and length of nociceptor neurons. We show that specific isoforms of the ecdysone receptor play critical cell autonomous roles in modulating the sensitivity of nociceptor neurons and may indicate human orthologs that represent targets for novel analgesic drugs.
Department of Biology, College of Arts and Sciences, University of New England, Biddeford, Maine, United States of America.
Aidan L
AL
McParland
Department of Biology, College of Arts and Sciences, University of New England, Biddeford, Maine, United States of America.
Taylor L
TL
Follansbee
Department of Biology, College of Arts and Sciences, University of New England, Biddeford, Maine, United States of America.
Gwendolyn D
GD
Vesenka
Department of Biology, College of Arts and Sciences, University of New England, Biddeford, Maine, United States of America.
Alexandra E
AE
Panaitiu
Department of Biology, College of Arts and Sciences, University of New England, Biddeford, Maine, United States of America.
Geoffrey K
GK
Ganter
D000818:Animals; D030801:Animals, Genetically Modified; D003712:Dendrites / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D009619:Nociceptors / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D013314:Stress, Mechanical; D013696:Temperature
D019476:Insect Proteins; D020033:Protein Isoforms; D011987:Receptors, Steroid; C055469:ecdysone receptor