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Chromatin Modulatory Proteins and Olfactory Receptor Signaling in the Refinement and Maintenance of Fruitless Expression in Olfactory Receptor Neurons.

Hueston CE, Olsen D, Li Q, Okuwa S, Peng B, Wu J, Volkan PC - PLoS Biol. (2016)

Bottom Line: This regulation requires the chromatin modulatory protein Alhambra (Alh).Our results highlight two feed-forward regulatory mechanisms with both developmentally hardwired and olfactory receptor activity-dependent components that establish and maintain fru expression in ORNs.Such a dual mechanism of fru regulation in ORNs might be a trait of neurons driving plastic aspects of sex-specific behaviors.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Duke University, Durham, North Carolina, United States of America.

ABSTRACT
During development, sensory neurons must choose identities that allow them to detect specific signals and connect with appropriate target neurons. Ultimately, these sensory neurons will successfully integrate into appropriate neural circuits to generate defined motor outputs, or behavior. This integration requires a developmental coordination between the identity of the neuron and the identity of the circuit. The mechanisms that underlie this coordination are currently unknown. Here, we describe two modes of regulation that coordinate the sensory identities of Drosophila melanogaster olfactory receptor neurons (ORNs) involved in sex-specific behaviors with the sex-specific behavioral circuit identity marker fruitless (fru). The first mode involves a developmental program that coordinately restricts to appropriate ORNs the expression of fru and two olfactory receptors (Or47b and Ir84a) involved in sex-specific behaviors. This regulation requires the chromatin modulatory protein Alhambra (Alh). The second mode relies on the signaling from the olfactory receptors through CamK and histone acetyl transferase p300/CBP to maintain ORN-specific fru expression. Our results highlight two feed-forward regulatory mechanisms with both developmentally hardwired and olfactory receptor activity-dependent components that establish and maintain fru expression in ORNs. Such a dual mechanism of fru regulation in ORNs might be a trait of neurons driving plastic aspects of sex-specific behaviors.

Show MeSH
Regulatory feed forward loops establish and maintain fru expression in the olfactory system.A multipotent precursor cell divides asymmetrically to generate at4 ORN cell types. In Or47b ORNs, a factor X is required to coactivate both Or47b and fru expression during development. In Or65a and Or88a ORNs, Alh, either directly or indirectly through repression of X, is required to repress both Or47b and fru. Once Or47b and fru expression is established in Or47b ORNs, OR function maintains fru expression through p300/CBP.
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pbio.1002443.g009: Regulatory feed forward loops establish and maintain fru expression in the olfactory system.A multipotent precursor cell divides asymmetrically to generate at4 ORN cell types. In Or47b ORNs, a factor X is required to coactivate both Or47b and fru expression during development. In Or65a and Or88a ORNs, Alh, either directly or indirectly through repression of X, is required to repress both Or47b and fru. Once Or47b and fru expression is established in Or47b ORNs, OR function maintains fru expression through p300/CBP.

Mentions: The finding that Creb-B overexpression, but Creb-B mutants, shows a dramatic reduction of fru expression is contradictory to the known function of Creb-B as a transcriptional activator. These results suggested that the effect of Creb-B overexpression on fru regulation could be indirect. Thus, we tested the possibility that Creb-B might be titrating a fru regulator that is found in limiting amounts in the ORNs. Creb proteins are known to interact with CBP/p300, which also interacts with many other transcription factors to maintain gene expression [45]. In addition, titrations effects on gene expression due to competition for limiting amounts of CBP/p300 was previously reported [48–52]. Since CBP/p300 is activated through phosphorylation by CamKI [43], we tested the hypothesis that p300 is required to maintain fru expression in Or47b and Ir84a ORNs. Similar to the CamKI mutants, and Creb-B overexpression experiments, an RNAi line targeting p300 showed a strong decrease in fru-positive Or47b ORNs (Fig 8D and 8E, S11 Fig). These results suggest that OR as well as CamK signaling, and CBP/p300 histone acetyl transferase function contribute to the maintenance of fru expression in Or47b ORNs (Fig 9).


Chromatin Modulatory Proteins and Olfactory Receptor Signaling in the Refinement and Maintenance of Fruitless Expression in Olfactory Receptor Neurons.

Hueston CE, Olsen D, Li Q, Okuwa S, Peng B, Wu J, Volkan PC - PLoS Biol. (2016)

Regulatory feed forward loops establish and maintain fru expression in the olfactory system.A multipotent precursor cell divides asymmetrically to generate at4 ORN cell types. In Or47b ORNs, a factor X is required to coactivate both Or47b and fru expression during development. In Or65a and Or88a ORNs, Alh, either directly or indirectly through repression of X, is required to repress both Or47b and fru. Once Or47b and fru expression is established in Or47b ORNs, OR function maintains fru expression through p300/CBP.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836687&req=5

pbio.1002443.g009: Regulatory feed forward loops establish and maintain fru expression in the olfactory system.A multipotent precursor cell divides asymmetrically to generate at4 ORN cell types. In Or47b ORNs, a factor X is required to coactivate both Or47b and fru expression during development. In Or65a and Or88a ORNs, Alh, either directly or indirectly through repression of X, is required to repress both Or47b and fru. Once Or47b and fru expression is established in Or47b ORNs, OR function maintains fru expression through p300/CBP.
Mentions: The finding that Creb-B overexpression, but Creb-B mutants, shows a dramatic reduction of fru expression is contradictory to the known function of Creb-B as a transcriptional activator. These results suggested that the effect of Creb-B overexpression on fru regulation could be indirect. Thus, we tested the possibility that Creb-B might be titrating a fru regulator that is found in limiting amounts in the ORNs. Creb proteins are known to interact with CBP/p300, which also interacts with many other transcription factors to maintain gene expression [45]. In addition, titrations effects on gene expression due to competition for limiting amounts of CBP/p300 was previously reported [48–52]. Since CBP/p300 is activated through phosphorylation by CamKI [43], we tested the hypothesis that p300 is required to maintain fru expression in Or47b and Ir84a ORNs. Similar to the CamKI mutants, and Creb-B overexpression experiments, an RNAi line targeting p300 showed a strong decrease in fru-positive Or47b ORNs (Fig 8D and 8E, S11 Fig). These results suggest that OR as well as CamK signaling, and CBP/p300 histone acetyl transferase function contribute to the maintenance of fru expression in Or47b ORNs (Fig 9).

Bottom Line: This regulation requires the chromatin modulatory protein Alhambra (Alh).Our results highlight two feed-forward regulatory mechanisms with both developmentally hardwired and olfactory receptor activity-dependent components that establish and maintain fru expression in ORNs.Such a dual mechanism of fru regulation in ORNs might be a trait of neurons driving plastic aspects of sex-specific behaviors.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Duke University, Durham, North Carolina, United States of America.

ABSTRACT
During development, sensory neurons must choose identities that allow them to detect specific signals and connect with appropriate target neurons. Ultimately, these sensory neurons will successfully integrate into appropriate neural circuits to generate defined motor outputs, or behavior. This integration requires a developmental coordination between the identity of the neuron and the identity of the circuit. The mechanisms that underlie this coordination are currently unknown. Here, we describe two modes of regulation that coordinate the sensory identities of Drosophila melanogaster olfactory receptor neurons (ORNs) involved in sex-specific behaviors with the sex-specific behavioral circuit identity marker fruitless (fru). The first mode involves a developmental program that coordinately restricts to appropriate ORNs the expression of fru and two olfactory receptors (Or47b and Ir84a) involved in sex-specific behaviors. This regulation requires the chromatin modulatory protein Alhambra (Alh). The second mode relies on the signaling from the olfactory receptors through CamK and histone acetyl transferase p300/CBP to maintain ORN-specific fru expression. Our results highlight two feed-forward regulatory mechanisms with both developmentally hardwired and olfactory receptor activity-dependent components that establish and maintain fru expression in ORNs. Such a dual mechanism of fru regulation in ORNs might be a trait of neurons driving plastic aspects of sex-specific behaviors.

Show MeSH