Limits...
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.

Show MeSH

Related in: MedlinePlus

The CSN suppresses Sens to inhibit neural differentiation of PWM bristles.(A, B) Overexpression of sens in C96-GAL4-driven UAS-flag-sens resulted in ectopic innervated bristles at the PWM of adult wings (A) and ectopic Hnt-positive cells at the PWM of wing discs 20–24 h APF (B). (C–F) Sens (red) expression was detected in CSN4 clones (C, C′), CSN5 clones (D, D′) and CSN6 RNAi knockdown by en-GAL4 (E, F) at the PWM 20–24 h APF. (G, H) Innervated bristles with sockets (arrowheads) appeared at the PWM of neur-GAL4 double knockdown of CSN1b and CSN7 (G), which were no longer detected when sens was also knocked down (H). (Insets in G, H) Enlarged figures showing single bristle and socket (arrowhead). (I, J) Double knockdown of CSN1b and CSN7 by neur-GAL4 resulted in accumulation of higher-level Hnt at the PWM, which was suppressed by sens knockdown (J). (K, K′) Ac (red) was not expressed in CSN4 clones in wing disc 18–22 h APF. (L, L′) Ectopic Sens-positive cells were detected in PWM clones for CSN4 in sc10-1  mutant disc 20–24 h APF.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4230841&req=5

pgen-1004760-g002: The CSN suppresses Sens to inhibit neural differentiation of PWM bristles.(A, B) Overexpression of sens in C96-GAL4-driven UAS-flag-sens resulted in ectopic innervated bristles at the PWM of adult wings (A) and ectopic Hnt-positive cells at the PWM of wing discs 20–24 h APF (B). (C–F) Sens (red) expression was detected in CSN4 clones (C, C′), CSN5 clones (D, D′) and CSN6 RNAi knockdown by en-GAL4 (E, F) at the PWM 20–24 h APF. (G, H) Innervated bristles with sockets (arrowheads) appeared at the PWM of neur-GAL4 double knockdown of CSN1b and CSN7 (G), which were no longer detected when sens was also knocked down (H). (Insets in G, H) Enlarged figures showing single bristle and socket (arrowhead). (I, J) Double knockdown of CSN1b and CSN7 by neur-GAL4 resulted in accumulation of higher-level Hnt at the PWM, which was suppressed by sens knockdown (J). (K, K′) Ac (red) was not expressed in CSN4 clones in wing disc 18–22 h APF. (L, L′) Ectopic Sens-positive cells were detected in PWM clones for CSN4 in sc10-1 mutant disc 20–24 h APF.

Mentions: Overexpression of Sens in epithelial cells can induce innervated bristles [3]. As shown, overexpression of Sens by C96-GAL4 along the wing margin induced bristles with sockets around the PWM (Figure 2A, arrowheads). Concomitantly, high levels of Hnt expressions were also detected (Figure 2B), confirming that ectopic Sens expression induces innervated bristles at the PWM.


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)

The CSN suppresses Sens to inhibit neural differentiation of PWM bristles.(A, B) Overexpression of sens in C96-GAL4-driven UAS-flag-sens resulted in ectopic innervated bristles at the PWM of adult wings (A) and ectopic Hnt-positive cells at the PWM of wing discs 20–24 h APF (B). (C–F) Sens (red) expression was detected in CSN4 clones (C, C′), CSN5 clones (D, D′) and CSN6 RNAi knockdown by en-GAL4 (E, F) at the PWM 20–24 h APF. (G, H) Innervated bristles with sockets (arrowheads) appeared at the PWM of neur-GAL4 double knockdown of CSN1b and CSN7 (G), which were no longer detected when sens was also knocked down (H). (Insets in G, H) Enlarged figures showing single bristle and socket (arrowhead). (I, J) Double knockdown of CSN1b and CSN7 by neur-GAL4 resulted in accumulation of higher-level Hnt at the PWM, which was suppressed by sens knockdown (J). (K, K′) Ac (red) was not expressed in CSN4 clones in wing disc 18–22 h APF. (L, L′) Ectopic Sens-positive cells were detected in PWM clones for CSN4 in sc10-1  mutant disc 20–24 h APF.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1004760-g002: The CSN suppresses Sens to inhibit neural differentiation of PWM bristles.(A, B) Overexpression of sens in C96-GAL4-driven UAS-flag-sens resulted in ectopic innervated bristles at the PWM of adult wings (A) and ectopic Hnt-positive cells at the PWM of wing discs 20–24 h APF (B). (C–F) Sens (red) expression was detected in CSN4 clones (C, C′), CSN5 clones (D, D′) and CSN6 RNAi knockdown by en-GAL4 (E, F) at the PWM 20–24 h APF. (G, H) Innervated bristles with sockets (arrowheads) appeared at the PWM of neur-GAL4 double knockdown of CSN1b and CSN7 (G), which were no longer detected when sens was also knocked down (H). (Insets in G, H) Enlarged figures showing single bristle and socket (arrowhead). (I, J) Double knockdown of CSN1b and CSN7 by neur-GAL4 resulted in accumulation of higher-level Hnt at the PWM, which was suppressed by sens knockdown (J). (K, K′) Ac (red) was not expressed in CSN4 clones in wing disc 18–22 h APF. (L, L′) Ectopic Sens-positive cells were detected in PWM clones for CSN4 in sc10-1 mutant disc 20–24 h APF.
Mentions: Overexpression of Sens in epithelial cells can induce innervated bristles [3]. As shown, overexpression of Sens by C96-GAL4 along the wing margin induced bristles with sockets around the PWM (Figure 2A, arrowheads). Concomitantly, high levels of Hnt expressions were also detected (Figure 2B), confirming that ectopic Sens expression induces innervated bristles at the PWM.

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