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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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Temporal regulation of Sens expression by CSN4.(A–C) Sens (red) expression in wild-type wing discs at the PWM. The expression gradually declined from 6–8 h APF (A) to 16–18 h APF (B), and was below detection 20–22 h APF (C). (D–E′) Sens (red) levels at the PWM 6–8 h APF were identical between CSN4 cells and neighboring CSN4/+ cells (D, D′), and were upregulated in CSN4 clones 16–18 h APF (E, E′).
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pgen-1004760-g005: Temporal regulation of Sens expression by CSN4.(A–C) Sens (red) expression in wild-type wing discs at the PWM. The expression gradually declined from 6–8 h APF (A) to 16–18 h APF (B), and was below detection 20–22 h APF (C). (D–E′) Sens (red) levels at the PWM 6–8 h APF were identical between CSN4 cells and neighboring CSN4/+ cells (D, D′), and were upregulated in CSN4 clones 16–18 h APF (E, E′).

Mentions: The activation of BR-Z1 expression in CSN mutants at pupal stages prefigures the timing in the upregulation of Sens. At the PWM, Sens was highly expressed in the precursors 6–8 h APF (Figure 5A) [4], declined to lower levels in lineage cells 16–18 h APF (Figure 5B), and became undetectable 20 h APF (Figure 5C). In CSN4 cells, while the Sens levels remained unchanged compared to neighboring control cells 6–8 h APF (Figure 5D, 5D′), Sens was upregulated at the pupal stage of 16–18 h APF (Figure 5E, 5E′), and the upregulation was maintained even 20–24 h APF (Figure 2C, 2C′). Taken together, the CSN downregulates BR-Z1 and Sens levels in a time-dependent manner, detected only 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)

Temporal regulation of Sens expression by CSN4.(A–C) Sens (red) expression in wild-type wing discs at the PWM. The expression gradually declined from 6–8 h APF (A) to 16–18 h APF (B), and was below detection 20–22 h APF (C). (D–E′) Sens (red) levels at the PWM 6–8 h APF were identical between CSN4 cells and neighboring CSN4/+ cells (D, D′), and were upregulated in CSN4 clones 16–18 h APF (E, E′).
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1004760-g005: Temporal regulation of Sens expression by CSN4.(A–C) Sens (red) expression in wild-type wing discs at the PWM. The expression gradually declined from 6–8 h APF (A) to 16–18 h APF (B), and was below detection 20–22 h APF (C). (D–E′) Sens (red) levels at the PWM 6–8 h APF were identical between CSN4 cells and neighboring CSN4/+ cells (D, D′), and were upregulated in CSN4 clones 16–18 h APF (E, E′).
Mentions: The activation of BR-Z1 expression in CSN mutants at pupal stages prefigures the timing in the upregulation of Sens. At the PWM, Sens was highly expressed in the precursors 6–8 h APF (Figure 5A) [4], declined to lower levels in lineage cells 16–18 h APF (Figure 5B), and became undetectable 20 h APF (Figure 5C). In CSN4 cells, while the Sens levels remained unchanged compared to neighboring control cells 6–8 h APF (Figure 5D, 5D′), Sens was upregulated at the pupal stage of 16–18 h APF (Figure 5E, 5E′), and the upregulation was maintained even 20–24 h APF (Figure 2C, 2C′). Taken together, the CSN downregulates BR-Z1 and Sens levels in a time-dependent manner, detected only 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