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The COP9 signalosome converts temporal hormone signaling to spatial restriction on neural competence.

Huang YC, Lu YN, Wu JT, Chien CT, Pi H - PLoS Genet. (2014)

Bottom Line: We found that the COP9 signalosome (CSN) suppresses the neural competence of non-innervated bristles at the PWM.Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level.We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Insitute of Molecular Biology, Academia Sinica, Taipei, Taiwan.

ABSTRACT
During development, neural competence is conferred and maintained by integrating spatial and temporal regulations. The Drosophila sensory bristles that detect mechanical and chemical stimulations are arranged in stereotypical positions. The anterior wing margin (AWM) is arrayed with neuron-innervated sensory bristles, while posterior wing margin (PWM) bristles are non-innervated. We found that the COP9 signalosome (CSN) suppresses the neural competence of non-innervated bristles at the PWM. In CSN mutants, PWM bristles are transformed into neuron-innervated, which is attributed to sustained expression of the neural-determining factor Senseless (Sens). The CSN suppresses Sens through repression of the ecdysone signaling target gene broad (br) that encodes the BR-Z1 transcription factor to activate sens expression. Strikingly, CSN suppression of BR-Z1 is initiated at the prepupa-to-pupa transition, leading to Sens downregulation, and termination of the neural competence of PWM bristles. The role of ecdysone signaling to repress br after the prepupa-to-pupa transition is distinct from its conventional role in activation, and requires CSN deneddylating activity and multiple cullins, the major substrates of deneddylation. Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level. We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.

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EcR regulation of BR-Z1 before and after the prepupa-to-pupa transition.(A–B′) DN-EcR-expressing clones (green) displayed BR-Z1 (red) downregulation at third-instar larval stages (A, A′) and upregulation 20–24 h APF (B, B′). (C–F) BR-Z1 (red) expression detected in wing discs of en-GAL4>UAS-DN-EcR; Tub-GAL80ts/+ 21–22 h APF. White arrowheads indicate anterior-posterior boundaries. BR-Z1 expression in the posterior compartment (bottom) was unaffected when animals were incubated at 18°C from larva to pupa (C), or at 18°C except during larva-to-prepupa transition (−4 to 3 h APF) at non-permissive temperatures (37°C for one hour and 29°C for six hours) (D). BR-Z1 levels were upregulated in pupae incubated at non-permissive temperatures 8–12 h APF (E) or 13–21 h APF (F). (G) A diagram showing the temperature regimen in animals shown in Figure C–F.
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pgen-1004760-g006: EcR regulation of BR-Z1 before and after the prepupa-to-pupa transition.(A–B′) DN-EcR-expressing clones (green) displayed BR-Z1 (red) downregulation at third-instar larval stages (A, A′) and upregulation 20–24 h APF (B, B′). (C–F) BR-Z1 (red) expression detected in wing discs of en-GAL4>UAS-DN-EcR; Tub-GAL80ts/+ 21–22 h APF. White arrowheads indicate anterior-posterior boundaries. BR-Z1 expression in the posterior compartment (bottom) was unaffected when animals were incubated at 18°C from larva to pupa (C), or at 18°C except during larva-to-prepupa transition (−4 to 3 h APF) at non-permissive temperatures (37°C for one hour and 29°C for six hours) (D). BR-Z1 levels were upregulated in pupae incubated at non-permissive temperatures 8–12 h APF (E) or 13–21 h APF (F). (G) A diagram showing the temperature regimen in animals shown in Figure C–F.

Mentions: To test whether ecdysone receptor activity is also involved in the switch from CSN-resistant to CSN-sensitive BR-Z1 suppression after the prepupa-to-pupa transition, the transcriptional activity of EcR was inactivated by the expression of dominant-negative EcRB1ΔC655F645A (DN-EcR) [49]. In DN-EcR expression clones, BR-Z1 expression in late larval wing discs was abolished (Figure 6A, 6A′), indicating that EcR positively regulates BR-Z1 expression [50]. In contrast, BR-Z1 expression was strongly induced in DN-EcR clones 20–24 h APF (Figure 6B, 6B′), indicating that transcriptionally active EcR represses BR-Z1 expression after the prepupa-to-pupa transition.


The COP9 signalosome converts temporal hormone signaling to spatial restriction on neural competence.

Huang YC, Lu YN, Wu JT, Chien CT, Pi H - PLoS Genet. (2014)

EcR regulation of BR-Z1 before and after the prepupa-to-pupa transition.(A–B′) DN-EcR-expressing clones (green) displayed BR-Z1 (red) downregulation at third-instar larval stages (A, A′) and upregulation 20–24 h APF (B, B′). (C–F) BR-Z1 (red) expression detected in wing discs of en-GAL4>UAS-DN-EcR; Tub-GAL80ts/+ 21–22 h APF. White arrowheads indicate anterior-posterior boundaries. BR-Z1 expression in the posterior compartment (bottom) was unaffected when animals were incubated at 18°C from larva to pupa (C), or at 18°C except during larva-to-prepupa transition (−4 to 3 h APF) at non-permissive temperatures (37°C for one hour and 29°C for six hours) (D). BR-Z1 levels were upregulated in pupae incubated at non-permissive temperatures 8–12 h APF (E) or 13–21 h APF (F). (G) A diagram showing the temperature regimen in animals shown in Figure C–F.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4230841&req=5

pgen-1004760-g006: EcR regulation of BR-Z1 before and after the prepupa-to-pupa transition.(A–B′) DN-EcR-expressing clones (green) displayed BR-Z1 (red) downregulation at third-instar larval stages (A, A′) and upregulation 20–24 h APF (B, B′). (C–F) BR-Z1 (red) expression detected in wing discs of en-GAL4>UAS-DN-EcR; Tub-GAL80ts/+ 21–22 h APF. White arrowheads indicate anterior-posterior boundaries. BR-Z1 expression in the posterior compartment (bottom) was unaffected when animals were incubated at 18°C from larva to pupa (C), or at 18°C except during larva-to-prepupa transition (−4 to 3 h APF) at non-permissive temperatures (37°C for one hour and 29°C for six hours) (D). BR-Z1 levels were upregulated in pupae incubated at non-permissive temperatures 8–12 h APF (E) or 13–21 h APF (F). (G) A diagram showing the temperature regimen in animals shown in Figure C–F.
Mentions: To test whether ecdysone receptor activity is also involved in the switch from CSN-resistant to CSN-sensitive BR-Z1 suppression after the prepupa-to-pupa transition, the transcriptional activity of EcR was inactivated by the expression of dominant-negative EcRB1ΔC655F645A (DN-EcR) [49]. In DN-EcR expression clones, BR-Z1 expression in late larval wing discs was abolished (Figure 6A, 6A′), indicating that EcR positively regulates BR-Z1 expression [50]. In contrast, BR-Z1 expression was strongly induced in DN-EcR clones 20–24 h APF (Figure 6B, 6B′), indicating that transcriptionally active EcR represses BR-Z1 expression after the prepupa-to-pupa transition.

Bottom Line: We found that the COP9 signalosome (CSN) suppresses the neural competence of non-innervated bristles at the PWM.Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level.We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Insitute of Molecular Biology, Academia Sinica, Taipei, Taiwan.

ABSTRACT
During development, neural competence is conferred and maintained by integrating spatial and temporal regulations. The Drosophila sensory bristles that detect mechanical and chemical stimulations are arranged in stereotypical positions. The anterior wing margin (AWM) is arrayed with neuron-innervated sensory bristles, while posterior wing margin (PWM) bristles are non-innervated. We found that the COP9 signalosome (CSN) suppresses the neural competence of non-innervated bristles at the PWM. In CSN mutants, PWM bristles are transformed into neuron-innervated, which is attributed to sustained expression of the neural-determining factor Senseless (Sens). The CSN suppresses Sens through repression of the ecdysone signaling target gene broad (br) that encodes the BR-Z1 transcription factor to activate sens expression. Strikingly, CSN suppression of BR-Z1 is initiated at the prepupa-to-pupa transition, leading to Sens downregulation, and termination of the neural competence of PWM bristles. The role of ecdysone signaling to repress br after the prepupa-to-pupa transition is distinct from its conventional role in activation, and requires CSN deneddylating activity and multiple cullins, the major substrates of deneddylation. Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level. We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.

Show MeSH
Related in: MedlinePlus