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Jun N-terminal kinase signaling makes a face

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

Schematic depiction of dpp expression in the (A) disc proper epithelium and (B) peripodial epithelium of third instar eye-antennal discs. The position of mapped primordia within the disc proper epithelium is summarized4,8,38 and indicated by: PAL - maxillary palps, RM - rostral membrane, VI - vibrissae, GE - gena, ANT - antennal field, and EYE - eye field. The position of the morphogenetic furrow is marked with arrowheads. dpp expression domains are depicted in blue. (C) Wild-type adult head compared to a (D) dpp head capsule mutant head induced by expression of dppRNAi33767 in the lateral peripodial domain using dpphc-Gal4. Note the disruption of ventral head structures including a smaller eye, loss of rostral membrane tissue, disordered sensory vibrissae, and missing maxillary palps. Solid arrow indicates wild-type vibrissae and solid arrowheads indicate wild-type palps. Open arrows indicate mutant vibrissae, and open arrowheads indicate missing palps. Third instar imaginal discs were stained with antibody to activated cleaved Caspase-3 to visualize apoptotic cells in (E) wild type and (F) a strong dpp head capsule mutant generated by the transheterozygous combination of TgRev46.1/ Df DTD2, P20. TgRev46.1 is a complex rearrangement with an inversion breakpoint within the dpp head capsule enhancer. Df DTD2, P20 is a large deficiency that removes dpp. Haplolethality is covered by a rescue construct that does not contain the dpp head capsule enhancer.5 Arrowheads indicate small apoptotic cell cluster, and arrow indicates anterior eye disc cell death aggregate. In all discs lateral is oriented to the left and medial to the right. (G) Model of signaling between the peripodial epithelium and the disc proper epithelium. Dpp plus JNK are required for Dpp to support cell survival in the disc proper. Dpp is also required for palp formation. In the absence of Dpp, high JNK activity is seen, which inhibits palp formation.
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f0001: Schematic depiction of dpp expression in the (A) disc proper epithelium and (B) peripodial epithelium of third instar eye-antennal discs. The position of mapped primordia within the disc proper epithelium is summarized4,8,38 and indicated by: PAL - maxillary palps, RM - rostral membrane, VI - vibrissae, GE - gena, ANT - antennal field, and EYE - eye field. The position of the morphogenetic furrow is marked with arrowheads. dpp expression domains are depicted in blue. (C) Wild-type adult head compared to a (D) dpp head capsule mutant head induced by expression of dppRNAi33767 in the lateral peripodial domain using dpphc-Gal4. Note the disruption of ventral head structures including a smaller eye, loss of rostral membrane tissue, disordered sensory vibrissae, and missing maxillary palps. Solid arrow indicates wild-type vibrissae and solid arrowheads indicate wild-type palps. Open arrows indicate mutant vibrissae, and open arrowheads indicate missing palps. Third instar imaginal discs were stained with antibody to activated cleaved Caspase-3 to visualize apoptotic cells in (E) wild type and (F) a strong dpp head capsule mutant generated by the transheterozygous combination of TgRev46.1/ Df DTD2, P20. TgRev46.1 is a complex rearrangement with an inversion breakpoint within the dpp head capsule enhancer. Df DTD2, P20 is a large deficiency that removes dpp. Haplolethality is covered by a rescue construct that does not contain the dpp head capsule enhancer.5 Arrowheads indicate small apoptotic cell cluster, and arrow indicates anterior eye disc cell death aggregate. In all discs lateral is oriented to the left and medial to the right. (G) Model of signaling between the peripodial epithelium and the disc proper epithelium. Dpp plus JNK are required for Dpp to support cell survival in the disc proper. Dpp is also required for palp formation. In the absence of Dpp, high JNK activity is seen, which inhibits palp formation.

Mentions: The adult Drosophila head is constructed largely from paired eye-antennal imaginal discs, sac-like structures comprising a columnar disc proper epithelium and a mostly squamous peripodial epithelium, separated by a lumen. The eye-antennal disc gives rise to 4 morphologically distinct organs (eye, antenna, ocelli, and maxillary palps) as well as the external cuticle (head capsule), and is subdivided during development into distinct morphological fields by the expression of transcription factors and signaling molecules. At third instar, dpp is expressed in a wedge on the lateral side of the antennal disc proper. Expression in the disc proper epithelium is also seen in the eye disc, within the morphogenetic furrow that will form the retina, and along the lateral and medial edges of that disc (Fig. 1A). In the peripodial layer, dpp is expressed in a diffuse area on the medial side of the eye-antennal disc, and in 2 stripes on the lateral side, along the future ventral side of the head (Fig. 1B). We focus on this lateral peripodial dpp expression, which arises in late 2nd instar eye-antennal discs and persists throughout the pupal period. Lateral peripodial expression is controlled by the homeotic transcription factor labial (lab)1 and the pair-rule gene odd-paired2,3 through an enhancer located in the 5′ end of the dpp gene.4 Like most post-embryonic dpp functions, the role of lateral peripodial dpp in ventral head morphogenesis was discovered through the recovery of cis-regulatory mutations that specifically disrupt this tissue specific expression.5dpp adult head mutations, referred to as head capsule mutations, cause defects of the ventral head. The eye is round instead of oval, due to loss of ventral ommatidia. Sensory vibrissae along the ventral margin of the eye are eliminated, or shifted and bunched. The “cheek” area: gena and rostral membrane tissue, which lies adjacent to the vibrissae, is malformed and reduced (Fig. 1D).5-7 Reduction, loss, or duplication of maxillary palps is also sometimes observed. The third instar imaginal discs appear grossly normal in size and morphology, but increased cell death is seen in the disc proper, and to a lesser extent in the peripodial epithelium in mutant discs.4 A fate map of adult cuticular structures within the disc, constructed by transplantation of imaginal disc fragments into adult abdomens, places the primordia of the majority of adult head structures, including those disrupted in ventral head mutants, within the disc proper.8 The observed cell death in the disc proper coupled with the placement of affected primordia within this tissue layer, suggest that peripodial dpp contributes to the morphogenesis of head structures in the underlying disc proper by supporting cell viability. However, this disc proper cell death is not correlated with any effects of Dpp on its known transcriptional targets. dpp target genes such as Daughters against dpp (Dad), an inhibitory factor induced by dpp signaling, and brinker (brk), a transcriptional repressor of dpp targets that is repressed by dpp signaling, display both peripodial and disc proper expression, but only peripodial expression of these genes is disrupted in ventral head mutations.4 Phosphorylation of the SMAD transcription factor, Mothers' against dpp (Mad) is another marker of canonical dpp signal transduction. Alterations in p-Mad expression are seen in the peripodial layer in mutant discs, but no clear spatial alterations are observed in disc proper p-Mad expression.Figure 1.


Jun N-terminal kinase signaling makes a face
Schematic depiction of dpp expression in the (A) disc proper epithelium and (B) peripodial epithelium of third instar eye-antennal discs. The position of mapped primordia within the disc proper epithelium is summarized4,8,38 and indicated by: PAL - maxillary palps, RM - rostral membrane, VI - vibrissae, GE - gena, ANT - antennal field, and EYE - eye field. The position of the morphogenetic furrow is marked with arrowheads. dpp expression domains are depicted in blue. (C) Wild-type adult head compared to a (D) dpp head capsule mutant head induced by expression of dppRNAi33767 in the lateral peripodial domain using dpphc-Gal4. Note the disruption of ventral head structures including a smaller eye, loss of rostral membrane tissue, disordered sensory vibrissae, and missing maxillary palps. Solid arrow indicates wild-type vibrissae and solid arrowheads indicate wild-type palps. Open arrows indicate mutant vibrissae, and open arrowheads indicate missing palps. Third instar imaginal discs were stained with antibody to activated cleaved Caspase-3 to visualize apoptotic cells in (E) wild type and (F) a strong dpp head capsule mutant generated by the transheterozygous combination of TgRev46.1/ Df DTD2, P20. TgRev46.1 is a complex rearrangement with an inversion breakpoint within the dpp head capsule enhancer. Df DTD2, P20 is a large deficiency that removes dpp. Haplolethality is covered by a rescue construct that does not contain the dpp head capsule enhancer.5 Arrowheads indicate small apoptotic cell cluster, and arrow indicates anterior eye disc cell death aggregate. In all discs lateral is oriented to the left and medial to the right. (G) Model of signaling between the peripodial epithelium and the disc proper epithelium. Dpp plus JNK are required for Dpp to support cell survival in the disc proper. Dpp is also required for palp formation. In the absence of Dpp, high JNK activity is seen, which inhibits palp formation.
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Related In: Results  -  Collection

License
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f0001: Schematic depiction of dpp expression in the (A) disc proper epithelium and (B) peripodial epithelium of third instar eye-antennal discs. The position of mapped primordia within the disc proper epithelium is summarized4,8,38 and indicated by: PAL - maxillary palps, RM - rostral membrane, VI - vibrissae, GE - gena, ANT - antennal field, and EYE - eye field. The position of the morphogenetic furrow is marked with arrowheads. dpp expression domains are depicted in blue. (C) Wild-type adult head compared to a (D) dpp head capsule mutant head induced by expression of dppRNAi33767 in the lateral peripodial domain using dpphc-Gal4. Note the disruption of ventral head structures including a smaller eye, loss of rostral membrane tissue, disordered sensory vibrissae, and missing maxillary palps. Solid arrow indicates wild-type vibrissae and solid arrowheads indicate wild-type palps. Open arrows indicate mutant vibrissae, and open arrowheads indicate missing palps. Third instar imaginal discs were stained with antibody to activated cleaved Caspase-3 to visualize apoptotic cells in (E) wild type and (F) a strong dpp head capsule mutant generated by the transheterozygous combination of TgRev46.1/ Df DTD2, P20. TgRev46.1 is a complex rearrangement with an inversion breakpoint within the dpp head capsule enhancer. Df DTD2, P20 is a large deficiency that removes dpp. Haplolethality is covered by a rescue construct that does not contain the dpp head capsule enhancer.5 Arrowheads indicate small apoptotic cell cluster, and arrow indicates anterior eye disc cell death aggregate. In all discs lateral is oriented to the left and medial to the right. (G) Model of signaling between the peripodial epithelium and the disc proper epithelium. Dpp plus JNK are required for Dpp to support cell survival in the disc proper. Dpp is also required for palp formation. In the absence of Dpp, high JNK activity is seen, which inhibits palp formation.
Mentions: The adult Drosophila head is constructed largely from paired eye-antennal imaginal discs, sac-like structures comprising a columnar disc proper epithelium and a mostly squamous peripodial epithelium, separated by a lumen. The eye-antennal disc gives rise to 4 morphologically distinct organs (eye, antenna, ocelli, and maxillary palps) as well as the external cuticle (head capsule), and is subdivided during development into distinct morphological fields by the expression of transcription factors and signaling molecules. At third instar, dpp is expressed in a wedge on the lateral side of the antennal disc proper. Expression in the disc proper epithelium is also seen in the eye disc, within the morphogenetic furrow that will form the retina, and along the lateral and medial edges of that disc (Fig. 1A). In the peripodial layer, dpp is expressed in a diffuse area on the medial side of the eye-antennal disc, and in 2 stripes on the lateral side, along the future ventral side of the head (Fig. 1B). We focus on this lateral peripodial dpp expression, which arises in late 2nd instar eye-antennal discs and persists throughout the pupal period. Lateral peripodial expression is controlled by the homeotic transcription factor labial (lab)1 and the pair-rule gene odd-paired2,3 through an enhancer located in the 5′ end of the dpp gene.4 Like most post-embryonic dpp functions, the role of lateral peripodial dpp in ventral head morphogenesis was discovered through the recovery of cis-regulatory mutations that specifically disrupt this tissue specific expression.5dpp adult head mutations, referred to as head capsule mutations, cause defects of the ventral head. The eye is round instead of oval, due to loss of ventral ommatidia. Sensory vibrissae along the ventral margin of the eye are eliminated, or shifted and bunched. The “cheek” area: gena and rostral membrane tissue, which lies adjacent to the vibrissae, is malformed and reduced (Fig. 1D).5-7 Reduction, loss, or duplication of maxillary palps is also sometimes observed. The third instar imaginal discs appear grossly normal in size and morphology, but increased cell death is seen in the disc proper, and to a lesser extent in the peripodial epithelium in mutant discs.4 A fate map of adult cuticular structures within the disc, constructed by transplantation of imaginal disc fragments into adult abdomens, places the primordia of the majority of adult head structures, including those disrupted in ventral head mutants, within the disc proper.8 The observed cell death in the disc proper coupled with the placement of affected primordia within this tissue layer, suggest that peripodial dpp contributes to the morphogenesis of head structures in the underlying disc proper by supporting cell viability. However, this disc proper cell death is not correlated with any effects of Dpp on its known transcriptional targets. dpp target genes such as Daughters against dpp (Dad), an inhibitory factor induced by dpp signaling, and brinker (brk), a transcriptional repressor of dpp targets that is repressed by dpp signaling, display both peripodial and disc proper expression, but only peripodial expression of these genes is disrupted in ventral head mutations.4 Phosphorylation of the SMAD transcription factor, Mothers' against dpp (Mad) is another marker of canonical dpp signal transduction. Alterations in p-Mad expression are seen in the peripodial layer in mutant discs, but no clear spatial alterations are observed in disc proper p-Mad expression.Figure 1.

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