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Jun N-terminal kinase signaling makes a face

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ABSTRACT

decapentaplegic (dpp), the Drosophila ortholog of BMP 2/4, directs ventral adult head morphogenesis through expression in the peripodial epithelium of the eye-antennal disc. This dpp expressing domain exerts effects both on the peripodial epithelium, and the underlying disc proper epithelium. We have uncovered a role for the Jun N-terminal kinase (JNK) pathway in dpp-mediated ventral head development. JNK activity is required for dpp's action on the disc proper, but in the absence of dpp expression, excessive JNK activity is produced, leading to specific loss of maxillary palps. In this review we outline our hypotheses on how dpp acts by both short range and longer range mechanisms to direct head morphogenesis and speculate on the dual role of JNK signaling in this process. Finally, we describe the regulatory control of dpp expression in the eye-antennal disc, and pose the problem of how the various expression domains of a secreted protein can be targeted to their specific functions.

No MeSH data available.


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Schematic diagram of the dpp gene. Coordinates from St. Johnston et al.37 are adjusted to reflect the actual genome sequence. The location of the exons for the 5 dpp transcripts are immediately below. Black boxes represent protein coding exons, white boxes represent non-coding exons. The disc region has been truncated for space considerations. The genomic positions of enhancer regions whose eye-antennal disc expression has been reported from transgenic constructs are indicated below. Enhancers include: the head capsule enhancer (SH53),4dpp-lacZ (BS3.0),38 the “blink” driver (dpp-Gal4),54 and Exelixis dpp-lacZ (Exel.2).39 An additional construct, dpp-Gal4.PS (85.8MX),55 located in an intron within the coding region, has been reported to express in the eye-antennal disc,56 but we are unable to replicate this result, and believe this construct has been confused with dpp.blink-Gal4.
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f0003: Schematic diagram of the dpp gene. Coordinates from St. Johnston et al.37 are adjusted to reflect the actual genome sequence. The location of the exons for the 5 dpp transcripts are immediately below. Black boxes represent protein coding exons, white boxes represent non-coding exons. The disc region has been truncated for space considerations. The genomic positions of enhancer regions whose eye-antennal disc expression has been reported from transgenic constructs are indicated below. Enhancers include: the head capsule enhancer (SH53),4dpp-lacZ (BS3.0),38 the “blink” driver (dpp-Gal4),54 and Exelixis dpp-lacZ (Exel.2).39 An additional construct, dpp-Gal4.PS (85.8MX),55 located in an intron within the coding region, has been reported to express in the eye-antennal disc,56 but we are unable to replicate this result, and believe this construct has been confused with dpp.blink-Gal4.

Mentions: In all imaginal discs dpp expression is discrete and has a highly dynamic temporal and spatial pattern. dpp is a large gene, with greater than 10 kb in the 5′ cis-regulatory region (shortvein, shv) and 25 kb of cis-regulatory information in the 3′ noncoding region (disk), as well as several large introns.37 All these different enhancers and numerous promoters regulate production of a single Dpp protein (Fig. 3). The disc proper expression of dpp seen at third instar is controlled by enhancer elements within the 3′ cis-regulatory region.38,39 These enhancers are poorly delineated, but appear to be both redundant, and not disc specific. The two known shv enhancer regions that control imaginal disc expression, the head capsule enhancer and the shortvein enhancer,5,40 are associated with dpp mutant phenotypes and dpp expression limited to specific discs. The majority of known dpp mutations disrupt the 5′ shv and 3′ disk cis-regulatory units, as dpp is haplo-insufficient, and true loss of function mutations are dominant embryonic lethals. Mutations that disrupt the 5′ cis-regulatory region do not interact genetically with those that disrupt the 3′ cis-regulatory region (an exception is 5′ mutations that knock out the 3 proximal promoters located in the shv region). At face value, this suggests that each pool of expressed, secreted Dpp acts separately from the others, even within the same disc. Many genetic analyses, demonstrating unique functions associated with each specific dpp expression domain, support this hypothesis. This is hard to reconcile with the observation that Dpp, localized by antibody, is broadly distributed and concentrates within the lumen that separates the peripodial and disc proper epithelia in both the eye-antennal and wing discs.41 How Dpp undergoes targeted dispersion remains a major question. Dpp dispersion has been studied most extensively in the wing disc. Planar dispersion has been modeled as passive extracellular diffusion, facilitated extracellular transport, transcytosis, and targeted delivery by cellular extensions.42-44 In addition to our work, others have documented evidence of vertical signaling from the peripodial layer to the disc proper, or disc proper to peripodial layer at different times during imaginal disc development.41,45-49 Mechanisms for such signaling may include protein-facilitated transport, vesicles, or cellular extensions.50,51 In addition, Dpp has been found in migratory cells such as hemocytes.52 Other Drosophila BMP members have been reported to be secreted into the general circulation by neuroendocrine cells.53 There is therefore an abundance of potential sources of Dpp for many tissues, which must be able to isolate and extract their specific BMP signal. In addition to facilitated transport, other mechanisms such as ligand processing, receptor accessibility, and various co-ligand/receptor availabilities and binding affinities may contribute to a cell's ability to decipher the Dpp signal intended uniquely for it. Establishing how this level of discrimination is achieved remains a major question in BMP signal transduction.Figure 3.


Jun N-terminal kinase signaling makes a face
Schematic diagram of the dpp gene. Coordinates from St. Johnston et al.37 are adjusted to reflect the actual genome sequence. The location of the exons for the 5 dpp transcripts are immediately below. Black boxes represent protein coding exons, white boxes represent non-coding exons. The disc region has been truncated for space considerations. The genomic positions of enhancer regions whose eye-antennal disc expression has been reported from transgenic constructs are indicated below. Enhancers include: the head capsule enhancer (SH53),4dpp-lacZ (BS3.0),38 the “blink” driver (dpp-Gal4),54 and Exelixis dpp-lacZ (Exel.2).39 An additional construct, dpp-Gal4.PS (85.8MX),55 located in an intron within the coding region, has been reported to express in the eye-antennal disc,56 but we are unable to replicate this result, and believe this construct has been confused with dpp.blink-Gal4.
© Copyright Policy - open-access
Related In: Results  -  Collection

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f0003: Schematic diagram of the dpp gene. Coordinates from St. Johnston et al.37 are adjusted to reflect the actual genome sequence. The location of the exons for the 5 dpp transcripts are immediately below. Black boxes represent protein coding exons, white boxes represent non-coding exons. The disc region has been truncated for space considerations. The genomic positions of enhancer regions whose eye-antennal disc expression has been reported from transgenic constructs are indicated below. Enhancers include: the head capsule enhancer (SH53),4dpp-lacZ (BS3.0),38 the “blink” driver (dpp-Gal4),54 and Exelixis dpp-lacZ (Exel.2).39 An additional construct, dpp-Gal4.PS (85.8MX),55 located in an intron within the coding region, has been reported to express in the eye-antennal disc,56 but we are unable to replicate this result, and believe this construct has been confused with dpp.blink-Gal4.
Mentions: In all imaginal discs dpp expression is discrete and has a highly dynamic temporal and spatial pattern. dpp is a large gene, with greater than 10 kb in the 5′ cis-regulatory region (shortvein, shv) and 25 kb of cis-regulatory information in the 3′ noncoding region (disk), as well as several large introns.37 All these different enhancers and numerous promoters regulate production of a single Dpp protein (Fig. 3). The disc proper expression of dpp seen at third instar is controlled by enhancer elements within the 3′ cis-regulatory region.38,39 These enhancers are poorly delineated, but appear to be both redundant, and not disc specific. The two known shv enhancer regions that control imaginal disc expression, the head capsule enhancer and the shortvein enhancer,5,40 are associated with dpp mutant phenotypes and dpp expression limited to specific discs. The majority of known dpp mutations disrupt the 5′ shv and 3′ disk cis-regulatory units, as dpp is haplo-insufficient, and true loss of function mutations are dominant embryonic lethals. Mutations that disrupt the 5′ cis-regulatory region do not interact genetically with those that disrupt the 3′ cis-regulatory region (an exception is 5′ mutations that knock out the 3 proximal promoters located in the shv region). At face value, this suggests that each pool of expressed, secreted Dpp acts separately from the others, even within the same disc. Many genetic analyses, demonstrating unique functions associated with each specific dpp expression domain, support this hypothesis. This is hard to reconcile with the observation that Dpp, localized by antibody, is broadly distributed and concentrates within the lumen that separates the peripodial and disc proper epithelia in both the eye-antennal and wing discs.41 How Dpp undergoes targeted dispersion remains a major question. Dpp dispersion has been studied most extensively in the wing disc. Planar dispersion has been modeled as passive extracellular diffusion, facilitated extracellular transport, transcytosis, and targeted delivery by cellular extensions.42-44 In addition to our work, others have documented evidence of vertical signaling from the peripodial layer to the disc proper, or disc proper to peripodial layer at different times during imaginal disc development.41,45-49 Mechanisms for such signaling may include protein-facilitated transport, vesicles, or cellular extensions.50,51 In addition, Dpp has been found in migratory cells such as hemocytes.52 Other Drosophila BMP members have been reported to be secreted into the general circulation by neuroendocrine cells.53 There is therefore an abundance of potential sources of Dpp for many tissues, which must be able to isolate and extract their specific BMP signal. In addition to facilitated transport, other mechanisms such as ligand processing, receptor accessibility, and various co-ligand/receptor availabilities and binding affinities may contribute to a cell's ability to decipher the Dpp signal intended uniquely for it. Establishing how this level of discrimination is achieved remains a major question in BMP signal transduction.Figure 3.

View Article: PubMed Central - PubMed

ABSTRACT

decapentaplegic (dpp), the Drosophila ortholog of BMP 2/4, directs ventral adult head morphogenesis through expression in the peripodial epithelium of the eye-antennal disc. This dpp expressing domain exerts effects both on the peripodial epithelium, and the underlying disc proper epithelium. We have uncovered a role for the Jun N-terminal kinase (JNK) pathway in dpp-mediated ventral head development. JNK activity is required for dpp's action on the disc proper, but in the absence of dpp expression, excessive JNK activity is produced, leading to specific loss of maxillary palps. In this review we outline our hypotheses on how dpp acts by both short range and longer range mechanisms to direct head morphogenesis and speculate on the dual role of JNK signaling in this process. Finally, we describe the regulatory control of dpp expression in the eye-antennal disc, and pose the problem of how the various expression domains of a secreted protein can be targeted to their specific functions.

No MeSH data available.


Related in: MedlinePlus