Academic journal article Genetics

Regulation of Aggression by Obesity-Linked Genes TfAP-2 and Twz through Octopamine Signaling in Drosophila

Academic journal article Genetics

Regulation of Aggression by Obesity-Linked Genes TfAP-2 and Twz through Octopamine Signaling in Drosophila

Article excerpt

ABSTRACT In Drosophila, the monoamine octopamine, through mechanisms that are not completely understood, regulates both aggression and mating behavior. Interestingly, our study demonstrates that the Drosophila obesity-linked homologs Transcription factor AP-2 (TfAP-2; TFAP2B in humans) and Tiwaz (Twz; KCTD15 in humans) interact to modify male behavior by controlling the expression of Tyramine b-hydroxylase and Vesicular monanime transporter, genes necessary for octopamine production and secretion. Furthermore, we reveal that octopamine in turn regulates aggression through the Drosophila cholecystokinin satiation hormone homolog Drosulfakinin (Dsk). Finally, we establish that TfAP-2 is expressed in octopaminergic neurons known to control aggressive behavior and that TfAP-2 requires functional Twz for its activity. We conclude that genetically manipulating the obesity-linked homologs TfAP-2 and Twz is sufficient to affect octopamine signaling, which in turn modulates Drosophila male behavior through the regulation of the satiation hormone Dsk.

AGGRESSION is an important behavioral trait enabling animals to fight for food, shelter, and mates or over territories where these resources can be found. The behav- ioral decision to be aggressive is in part controlled by systems that also regulate metabolism, such as the monoamine sys- tem (Dierick and Greenspan 2007; Hoyer et al. 2008; Zhou et al. 2008; Alekseyenko et al. 2010). In the fruit fly Drosophila melanogaster, it was determined that a major regulator of male aggressive and mating behavior is the noradrenaline analog, octopamine (Baier et al. 2002; Hoyer et al. 2008; Zhou et al. 2008, 2012; Certel et al. 2010; Erion et al. 2012). In addition, the monoamines dopamine and serotonin have been linked to the regulation of aggressive behavior (Lucki 1998; Baier et al. 2002; Alekseyenko et al. 2010, 2013; Belsare et al. 2010). Yet the molecular mechanisms under- lying aggression are still not fully understood.

The human genes Transcription factor AP-2 (TFAP2B) (encoding AP-2b)andKCTD15 have been identified as novel loci associated with obesity (Bauer et al. 2009; Renstrom et al. 2009; Willer et al. 2009; Zhao et al. 2011), although it is still not known how they regulate obesity at the molecular level. TFAP2B is a member of the AP-2 family of transcription factors, key regulators of various developmental processes (Eckert et al. 2005; Meng et al. 2010; Wenke and Bosserhoff 2010), and in mice it was demonstrated that TFAP2B is necessary for the proper development of peripheral and cen- tral nervous system noradrenergic neurons (Hong et al. 2008; Schmidt et al. 2011). KCTD15 belongs to a family of potassium-channel tetramerization domain-containing pro- teins. In zebrafish embryos, Kctd15 functions to inhibit the activity of AP-2a to restrict neural crest formation, although the exact mechanism of this inhibition is unknown (Dutta and Dawid 2010; Zarelli and Dawid 2013).

In Drosophila, TFAP2B is highly conserved, encoded by the gene TfAP-2. There is preliminary evidence from a yeast two-hybrid screen that TfAP-2 associates with the Drosophila KCTD15 homolog CG10440, which we have named Tiwaz (Twz; see Materials and Methods) (Giot et al. 2003). Further- more, both genes are highly expressed in the central nervous system (Chintapalli et al. 2007). In mice, TFAP2B regulates the noradrenergic system, and we asked if TfAP-2 and Twz could be involved in regulating behavior through octopamine signaling, a central controller of aggression in Drosophila (Hoyer et al. 2008; Zhou et al. 2008). Octopaminergic neurons are known to innervate the insulin-producing cells located in the Par intercerebralis of the Drosophila brain (Crocker et al. 2010). Intriguingly, it was recently discovered that these insulin-producing cells also produce the Drosophila homolog of cholecystokinin (CCK), known as Drosulfakinin (Dsk) (Söderberg et al. 2012), and in rodents levels of the satiation hormone CCK are correlated with aggression (Zwanzger et al. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.