Tailless and Atrophin control Drosophila aggression by regulating neuropeptide signalling in the pars intercerebralis

Davis, Shaun; Thomas, Amanda L.; Nomie, Krystle; Huang, Longwen; Dierick, Herman A.

doi:10.1038/ncomms4177

Cited by 47 publications

(45 citation statements)

References 72 publications

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“…Mouse and fly Nr2e1/tll proteins share a conserved DNA binding motif, which we identified as significantly enriched in the promoter regions of DEGs in all three species. These results are consistent with previous studies showing that Nr2e1/tll proteins have similar regulatory targets (55,56) and are known to play a conserved role in aggression (57). Portions of the mouse hypothalamus and the stickleback diencephalon belong to the vertebrate brain social behavior network, a series of connected brain regions that control multiple social behaviors, including aggression (58).…”

Section: Discussionsupporting

confidence: 82%

Neuromolecular responses to social challenge: Common mechanisms across mouse, stickleback fish, and honey bee

Rittschof

Bukhari

Sloofman

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

142

196

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Certain complex phenotypes appear repeatedly across diverse species due to processes of evolutionary conservation and convergence. In some contexts like developmental body patterning, there is increased appreciation that common molecular mechanisms underlie common phenotypes; these molecular mechanisms include highly conserved genes and networks that may be modified by lineage-specific mutations. However, the existence of deeply conserved mechanisms for social behaviors has not yet been demonstrated. We used a comparative genomics approach to determine whether shared neuromolecular mechanisms could underlie behavioral response to territory intrusion across species spanning a broad phylogenetic range: house mouse (Mus musculus), stickleback fish (Gasterosteus aculeatus), and honey bee (Apis mellifera). Territory intrusion modulated similar brain functional processes in each species, including those associated with hormone-mediated signal transduction and neurodevelopment. Changes in chromosome organization and energy metabolism appear to be core, conserved processes involved in the response to territory intrusion. We also found that several homologous transcription factors that are typically associated with neural development were modulated across all three species, suggesting that shared neuronal effects may involve transcriptional cascades of evolutionarily conserved genes. Furthermore, immunohistochemical analyses of a subset of these transcription factors in mouse again implicated modulation of energy metabolism in the behavioral response. These results provide support for conserved genetic "toolkits" that are used in independent evolutions of the response to social challenge in diverse taxa.genetic hotspot | NF-κB signaling | brain metabolism | aggression S imilar phenotypes can have a shared molecular basis, even among distantly related species (1-3). This phenomenon has been observed for an array of traits, including morphological adaptations like coat color or wing patterning, rapid adaptations like drug resistance, and artificially selected phenological traits like flowering time (reviewed in ref. 2). Shared molecular mechanisms can arise convergently as a result of de novo mutations at genetic hotspots (2) or as a result of conservation. Both of these processes result in "genetic toolkits" or genes that are repeatedly used over evolutionary time to give rise to similar phenotypes (3). The phenomenon of genetic toolkits challenges fundamental notions about evolutionary convergence, conservation, and the origins of biodiversity.The role of genetic toolkits in shaping behavioral phenotypes is unclear (4, 5). Behaviors are typically polygenic (6) and they show great nuance and plasticity within a species, raising the possibility that cross-species similarities in behavior are superficial. Social behaviors in particular present a challenge to the genetic toolkit concept: these behaviors are critical to survival and reproductive success, but across species there is significant variation in the contexts for an...

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Section: Discussionsupporting

confidence: 82%

Neuromolecular responses to social challenge: Common mechanisms across mouse, stickleback fish, and honey bee

Rittschof

Bukhari

Sloofman

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

142

196

View full text Add to dashboard Cite

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“…These important roles in neural identity and boundary formation appear to be well-conserved in other animals. Loss of tll in the adult fly pars intercerebralis leads to a loss of neuropeptide expression and increased aggression, although the specific developmental effect in this part of the brain has not been described [150]. …”

Section: Tll/nhr-67/tlx (Nr2e1)mentioning

confidence: 99%

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

Bodofsky¹,

Koitz²,

Wightman³

2017

Nuclear Receptor Research

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The nuclear receptor gene family includes 18 members that are broadly conserved among multiple disparate animal phyla, indicating that they trace their evolutionary origins to the time at which animal life arose. Typical nuclear receptors contain two major domains: a DNA-binding domain and a C-terminal domain that may bind a lipophilic hormone. Many of these nuclear receptors play varied roles in animal development, including coordination of life cycle events and cellular differentiation. The well-studied genetic model systems of Drosophila, C. elegans, and mouse permit an evaluation of the extent to which nuclear receptor function in development is conserved or exapted (repurposed) over animal evolution. While there are some specific examples of conserved functions and pathways, there are many clear examples of exaptation. Overall, the evolutionary theme of exaptation appears to be favored over strict functional conservation. Despite strong conservation of DNA-binding domain sequences and activity, the nuclear receptors prove to be highly-flexible regulators of animal development.

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“…Atrophin proteins selectively bind to a number of repressor orphan nuclear receptors and influence their physiological activities (Wang et al 2006Zhang et al 2006;Haecker et al 2007;Escher et al 2009;Vilhais-Neto et al 2010;Davis et al 2014). To date, the functional interaction between dTLX and dAtrophin has been best characterized in Drosophila using genetic and biochemical analysis (Wang et al 2006;Haecker et al 2007;Davis et al 2014). Atrophin proteins bind to TLX via their C-terminal region, which contains the highly conserved Atro box motif ( Fig.…”

mentioning

confidence: 99%

Structural basis for corepressor assembly by the orphan nuclear receptor TLX

Zhi

Zhou

et al. 2015

Genes Dev.

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The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX-Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression.

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Tailless and Atrophin control Drosophila aggression by regulating neuropeptide signalling in the pars intercerebralis

Cited by 47 publications

References 72 publications

Neuromolecular responses to social challenge: Common mechanisms across mouse, stickleback fish, and honey bee

Neuromolecular responses to social challenge: Common mechanisms across mouse, stickleback fish, and honey bee

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

Structural basis for corepressor assembly by the orphan nuclear receptor TLX

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