Drosophila taoControls Mushroom Body Development and Ethanol-Stimulated Behavior throughpar-1

Abstract

In both mammalian and insect models of ethanol-induced behavior, low doses of ethanol stimulate locomotion. However, the mechanisms of the stimulant effects of ethanol on the CNS are mostly unknown. We have identified tao, encoding a serine-threonine kinase of the Ste20 family, as a gene necessary for ethanol-induced locomotor hyperactivity in Drosophila. Mutations in tao also affect behavioral responses to cocaine and nicotine, making flies resistant to the effects of both drugs. We show that tao function is required during the development of the adult nervous system and that tao mutations cause defects in the development of central brain structures, including the mushroom body. Silencing of a subset of mushroom body neurons is sufficient to reduce ethanol-induced hyperactivity, revealing the mushroom body as an important locus mediating the stimulant effects of ethanol. We also show that mutations in par-1 suppress both the mushroom body morphology and behavioral phenotypes of tao mutations and that the phosphorylation state of the microtubule-binding protein Tau can be altered by RNA interference knockdown of tao, suggesting that tao and par-1 act in a pathway to control microtubule dynamics during neural development.

Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex

“…S3e). These results strongly support the role of TAO2 in axon elongation in the mouse in vivo , as was previously reported in Drosophila 19 .…”

“…1c). This pattern of TAO2 expression suggests that TAO2 may act as a coordinator of actin and microtubule dynamics 19 .…”

The Genetics of Alcohol Responses of Invertebrate Model Systems

“…The mushroom bodies are structures involved in associative learning in flies (Shuai et al, 2010), and they undergo major reorganization and restructuring during pupal metamorphosis (Armstrong, de Belle, Wang, & Kaiser, 1998). Unlike some of the previously mentioned regulators of actin dynamics, Tao is required during development and not in the adult fly (King et al, 2011), indicating that the kinase is involved in setting up ethanol-responsive circuitry. Tao acts through the Jun N-terminal MAP kinase, JNK, to regulate ethanol-induced hyperactivity and brain morphology (Kapfhamer et al, 2012).…”

“…Loss of Tao leads to a decrease in ethanol-induced hyperactivity in flies and also to morphological defects in the brain, including the mushroom III. GENE AND BEHAVIOR bodies (King et al, 2011). The mushroom bodies are structures involved in associative learning in flies (Shuai et al, 2010), and they undergo major reorganization and restructuring during pupal metamorphosis (Armstrong, de Belle, Wang, & Kaiser, 1998).…”

From Signaling Pathways to Behavior

“…In addition to ERK1/2, other MAPKs have also been found to regulate the acute effects of alcohol in flies. A Drosophila genetic screen revealed that a loss-offunction mutation of the Tao gene, encoding a putative MAP3K belonging to a subfamily of the sterile 20 protein (Ste20p) kinases, reduced alcohol-induced locomotor hyperactivity (King et al, 2011). There are three mammalian orthologs of Drosophila tao: TaoK1, TaoK2, and TaoK3.…”