scholarly journals The relaxin receptor Lgr3 mediates growth coordination and developmental delay during Drosophila melanogaster imaginal disc regeneration

2015 ◽  
Author(s):  
Jacob S. Jaszczak ◽  
Jacob B. Wolpe ◽  
Rajan Bhandari ◽  
Rebecca G. Jaszczak ◽  
Adrian Halme
Keyword(s):  
Drosophila Melanogaster ◽  
Developmental Delay ◽  
Imaginal Disc ◽  
Imaginal Discs ◽  
Prothoracic Gland ◽  
Disc Regeneration ◽  
Relaxin Family ◽  
Dependent Growth ◽  
Oxide Synthase ◽  
Relaxin Receptor

Damage to Drosophila melanogaster imaginal discs activates a regeneration checkpoint that 1) extends larval development and 2) coordinates the regeneration of the damaged disc with the growth of undamaged discs. These two systemic responses to damage are both mediated by Dilp8, a member of the insulin/IGF/relaxin family of peptide hormones, which is released by regenerating imaginal discs. Growth coordination between regenerating and undamaged imaginal discs is dependent on Dilp8 activation of NOS in the prothoracic gland (PG), which slows the growth of undamaged discs by limiting ecdysone synthesis. Here we demonstrate that the Drosophila relaxin receptor homologue Lgr3, a leucine-rich repeat-containing G-protein coupled receptor, is required for Dilp8-dependent growth coordination and developmental delay during the regeneration checkpoint. Lgr3 regulates these responses to damage via distinct mechanisms in different tissues. Using tissue-specific RNAi disruption of Lgr3 expression, we show that Lgr3 functions in the PG upstream of nitric oxide synthase (NOS), and is necessary for NOS activation and growth coordination during the regeneration checkpoint. When Lgr3 is depleted from neurons, imaginal disc damage no longer produces either developmental delay or growth inhibition. To reconcile these discrete tissue requirements for Lgr3 during regenerative growth coordination, we demonstrate that Lgr3 activity in the both the CNS and PG is necessary for NOS activation in the PG following damage. Together, these results identify new roles for a relaxin receptor in mediating damage signaling to regulate growth and developmental timing.

scholarly journals Nitric oxide regulates growth coordination during regeneration

2015 ◽  
Author(s):  
Jacob S. Jaszczak ◽  
Jacob B. Wolpe ◽  
Anh Q. Dao ◽  
Adrian Halme
Keyword(s):  
Nitric Oxide ◽  
Developmental Delay ◽  
Growth Control ◽  
Tissue Growth ◽  
Prothoracic Gland ◽  
Growth Status ◽  
Developmental Progression ◽  
Relaxin Family ◽  
Dependent Growth ◽  
Oxide Synthase

Mechanisms that coordinate the growth of different tissues during development are essential for producing adult animals with proper organ proportion. Here we describe a pathway through which tissues communicate with each other to coordinate growth. DuringDrosophila melanogasterlarval development, damage to imaginal discs activates a regeneration checkpoint that produces both a delay in developmental timing and slows the growth of undamaged tissues, coordinating regeneration of the damaged tissue with developmental progression and overall growth. Both developmental delay and growth control are mediated by secretion of the insulin/relaxin family peptide Dilp8 from regenerating tissues. Here we demonstrate that Dilp8-dependent growth coordination between regenerating and undamaged tissues, but not developmental delay, requires the activity of nitric oxide synthase (NOS) in the prothoracic gland. NOS limits the growth of undamaged tissues by reducing ecdysone biosynthesis, a requirement for imaginal disc growth during both the regenerative checkpoint and normal development. Therefore, NOS activity in the prothoracic gland translates information about the growth status of individual tissues into coordinated tissue growth through the regulation of endocrine signals.

scholarly journals Ecdysone regulates the Drosophila imaginal disc epithelial barrier, determining the length of regeneration checkpoint delay

Development ◽  
2021 ◽  
Vol 148 (6) ◽  
Author(s):  
Danielle DaCrema ◽  
Rajan Bhandari ◽  
Faith Karanja ◽  
Ryunosuke Yano ◽  
Adrian Halme
Keyword(s):  
Imaginal Disc ◽  
Steroid Hormone ◽  
Prothoracic Gland ◽  
Epithelial Barrier ◽  
Septate Junctions ◽  
Barrier Permeability ◽  
The Third ◽  
Developmental Progression ◽  
Relaxin Family ◽  
The Brain

ABSTRACT Regeneration of Drosophila imaginal discs, larval precursors to adult tissues, activates a regeneration checkpoint that coordinates regenerative growth with developmental progression. This regeneration checkpoint results from the release of the relaxin-family peptide Dilp8 from regenerating imaginal tissues. Secreted Dilp8 protein is detected within the imaginal disc lumen, in which it is separated from its receptor target Lgr3, which is expressed in the brain and prothoracic gland, by the disc epithelial barrier. Here, we demonstrate that following damage the imaginal disc epithelial barrier limits Dilp8 signaling and the duration of regeneration checkpoint delay. We also find that the barrier becomes increasingly impermeable to the transepithelial diffusion of labeled dextran during the second half of the third instar. This change in barrier permeability is driven by the steroid hormone ecdysone and correlates with changes in localization of Coracle, a component of the septate junctions that is required for the late-larval impermeable epithelial barrier. Based on these observations, we propose that the imaginal disc epithelial barrier regulates the duration of the regenerative checkpoint, providing a mechanism by which tissue function can signal the completion of regeneration.

A Drosophila rotund transcript expressed during spermatogenesis and imaginal disc morphogenesis encodes a protein which is similar to human Rac GTPase-activating (racGAP) proteins

1992 ◽  
Vol 12 (11) ◽  
pp. 5111-5122
Author(s):  
M Agnel ◽  
L Röder ◽  
C Vola ◽  
R Griffin-Shea
Keyword(s):  
Cell Death ◽  
Drosophila Melanogaster ◽  
Sequence Analysis ◽  
Imaginal Disc ◽  
Germ Line ◽  
Imaginal Discs ◽  
Mutant Phenotype ◽  
Physical Characterization ◽  
Rac Gtpase

The rotund (rn) locus of Drosophila melanogaster at cytogenetic position 84D3,4 has been isolated and cloned on the basis of the mutant phenotype: an absence of structures in the subdistal regions of the appendages. The shortened appendages are the consequence of a localized cell death in the imaginal discs, precursors of the adult appendages. Physical characterization of the rn locus has demonstrated that it is relatively large, occupying a minimum of 50 kb. There are two major transcripts of 1.7 kb (m1.7) and 5.3 kb (m5.3). We present here the sequence analysis of m1.7 and its putative product, rnprot1.7, and show that rnprot1.7 is similar to the product of the human n-chimaerin gene, which is expressed in brain and testes. Recently, the GAP activity of n-chimaerin was demonstrated and shown to be specific for the Rac subfamily of the Ras oncoproteins. The Rac proteins have been implicated in the regulation of secretory processes. In addition to being expressed in the imaginal discs, the m1.7 racGAP transcript was detected in developmentally specific germ line cells of the testes, the primary spermatocytes.

Gene expression during imaginal disc regeneration detected using enhancer-sensitive P-elements

Development ◽  
1993 ◽  
Vol 117 (4) ◽  
pp. 1287-1297 ◽  
Author(s):  
W.J. Brook ◽  
L.M. Ostafichuk ◽  
J. Piorecky ◽  
M.D. Wilkinson ◽  
D.J. Hodgetts ◽  
...  
Keyword(s):  
Cell Death ◽  
Imaginal Disc ◽  
Expression Patterns ◽  
Imaginal Discs ◽  
P Element ◽  
Temperature Sensitive ◽  
Lethal Mutant ◽  
Disc Regeneration ◽  
Lac Z ◽  
Regeneration Blastema

When imaginal disc fragments from Drosophila are cultured in adult female hosts, they either duplicate the part of the pattern specified by the fate map, or regenerate to replace the missing part. The new tissue is added by proliferation of a small number of cells from the cut edge, brought together when the wound heals to form a regeneration blastema. Specification of the new pattern has been explained by assuming interactions among cells of different positional value in the regeneration blastema. In order to identify genes which might mediate these events, we screened over eight hundred independently isolated autosomal insertions of an enhancer-sensitive P-element, for altered lac-z expression in regenerating discs following cell death induced by a temperature-sensitive cell-lethal mutation. Two further screens divided the positive lines into four groups based on appropriate timing of the lac-z response in the cell-lethal mutant background and the expected response to an alternate source of cell death. Expression in wing disc fragments cultured in vivo was most frequent in the target class defined by the screens. In this direct test, lac-z expression was found in 23 lines and in most cases was spatially and temporally correlated with the formation of the regeneration blastema. Our results suggest a very substantial transcriptional response during the early stages of imaginal disc regeneration. lac-z expression in control imaginal discs, embryos and adult ovaries of the positive lines was also assayed. The selected insertions included: a small class expressed only in discs undergoing regeneration and apparently not at any other stage, possibly representing genes active exclusively in regeneration; a larger class expressed in the embryo or during oogenesis, but not normally in imaginal discs, as expected for functions recruited from earlier stages of the developmental program; and finally a class with spatially patterned expression in normal discs. This class included several insertions with expression associated with compartment boundaries, including one at the decapentaplegic (dpp), and one at the crumbs (crb) locus, a growth factor homologue, and an EGF-repeat gene respectively. Some of the expression patterns observed in cultured disc fragments provide evidence for cell communication in the regeneration blastema.

scholarly journals A Drosophila rotund transcript expressed during spermatogenesis and imaginal disc morphogenesis encodes a protein which is similar to human Rac GTPase-activating (racGAP) proteins.

1992 ◽  
Vol 12 (11) ◽  
pp. 5111-5122 ◽  
Author(s):  
M Agnel ◽  
L Röder ◽  
C Vola ◽  
R Griffin-Shea
Keyword(s):  
Cell Death ◽  
Drosophila Melanogaster ◽  
Sequence Analysis ◽  
Imaginal Disc ◽  
Germ Line ◽  
Imaginal Discs ◽  
Mutant Phenotype ◽  
Physical Characterization ◽  
Rac Gtpase

The rotund (rn) locus of Drosophila melanogaster at cytogenetic position 84D3,4 has been isolated and cloned on the basis of the mutant phenotype: an absence of structures in the subdistal regions of the appendages. The shortened appendages are the consequence of a localized cell death in the imaginal discs, precursors of the adult appendages. Physical characterization of the rn locus has demonstrated that it is relatively large, occupying a minimum of 50 kb. There are two major transcripts of 1.7 kb (m1.7) and 5.3 kb (m5.3). We present here the sequence analysis of m1.7 and its putative product, rnprot1.7, and show that rnprot1.7 is similar to the product of the human n-chimaerin gene, which is expressed in brain and testes. Recently, the GAP activity of n-chimaerin was demonstrated and shown to be specific for the Rac subfamily of the Ras oncoproteins. The Rac proteins have been implicated in the regulation of secretory processes. In addition to being expressed in the imaginal discs, the m1.7 racGAP transcript was detected in developmentally specific germ line cells of the testes, the primary spermatocytes.

scholarly journals Ecdysone regulates the Drosophila imaginal disc epithelial barrier, determining the duration of regeneration checkpoint delay

2020 ◽  
Author(s):  
Danielle DaCrema ◽  
Rajan Bhandari ◽  
Faith Karanja ◽  
Ryunosuke Yano ◽  
Adrian Halme
Keyword(s):  
Imaginal Disc ◽  
Larval Instar ◽  
Prothoracic Gland ◽  
Epithelial Barrier ◽  
Developmental Progression ◽  
Relaxin Family ◽  
Larval Hemolymph ◽  
Summary Statement ◽  
The Brain ◽  
Ecdysone Signaling

AbstractRegeneration of Drosophila imaginal discs, larval precursors to adult tissues, produces a systemic response, a regeneration checkpoint that coordinates regenerative growth with developmental progression. This regeneration checkpoint is coordinated by the release of the relaxin-family peptide Dilp8 from regenerating tissues. Secreted Dilp8 protein can be detected within the imaginal disc lumen. The disc epithelium separates from the lumen from the larval hemolymph and the targets for Dilp8 activity in the brain and prothoracic gland. Here we demonstrate that the imaginal disc epithelial barrier limits Dilp8 signaling and checkpoint delay. We also observe that the wing imaginal disc barrier becomes more restrictive during development, becoming impermeable only at end of the final larval instar. This change in barrier permeability is driven by the steroid hormone ecdysone and correlates with changes in localization of Coracle, a component of the septate junctions that is required for the late, impermeable epithelial barrier. Based on these observations, we propose that the imaginal disc epithelial barrier regulates the duration of the regenerative checkpoint, providing a mechanism by which tissue function can signal the completion of regeneration.Summary StatementEcdysone signaling directs the Drosophila third instar imaginal disc epithelial barrier to mature, becoming more restrictive. This mature barrier limits Dilp8 signaling and determines the duration of the regeneration checkpoint.

scholarly journals Analysis in Drosophila melanogaster of the Interaction Between Sex Combs Reduced and Extradenticle Activity in the Determination of Tarsus and Arista Identity

Genetics ◽  
1998 ◽  
Vol 150 (1) ◽  
pp. 189-198
Author(s):  
Anthony Percival-Smith ◽  
Danielle J Hayden
Keyword(s):  
Drosophila Melanogaster ◽  
Imaginal Disc ◽  
Imaginal Discs ◽  
Nuclear Accumulation ◽  
Sex Combs Reduced ◽  
Sex Combs ◽  
Disc Cells

Abstract Sex Combs Reduced (SCR) activity is proposed to be required cell nonautonomously for determination of tarsus identity, and Extradenticle (EXD) activity is required cell autonomously for determination of arista identity. Using the ability of Proboscipedia to inhibit the SCR activity required for determination of tarsus identity, we found that loss-of-EXD activity is epistatic to loss-of-SCR activity in tarsus vs. arista determination. This suggests that in the sequence leading to arista determination SCR activity is OFF while EXD activity is ON, and in the sequence leading to tarsus determination SCR activity is ON, which turns EXD activity OFF. Immunolocalization of EXD in early third-instar larval imaginal discs reveals that EXD is localized in the nuclei of antennal imaginal disc cells and localized in the cytoplasm of distal imaginal leg disc cells. We propose that EXD localized to the nucleus suppresses tarsus determination and activates arista determination. We further propose that in the mesodermal adepithelial cells of the leg imaginal discs, SCR is required for the synthesis of a tarsus-inducer that when secreted acts on the ectoderm cells inhibiting nuclear accumulation of EXD, such that tarsus determination is no longer suppressed and arista determination is no longer activated.

Imaginal disc-autonomous expression of a defect in sensory bristle patterning caused by the lethal(3)ecdysoneless1 (1(3)ecd1) mutation of Drosophila melanogaster

Development ◽  
1989 ◽  
Vol 106 (2) ◽  
pp. 347-354 ◽  
Author(s):  
T.J. Sliter
Keyword(s):  
Drosophila Melanogaster ◽  
Imaginal Disc ◽  
Early Period ◽  
Prothoracic Gland ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Molting Hormone ◽  
Sense Organs ◽  
Puparium Formation ◽  
Sensory Bristles

The temperature-sensitive mutation 1(3)ecd1 of Drosophila melanogaster is known to autonomously impair the ability of the larval prothoracic gland to produce the steroid molting hormone ecdysone in response to stimulation by the tropic neuropeptide prothoracicotropic hormone. It is shown that autonomous expression of the 1(3)ecd1 mutation in metamorphosing imaginal tissues disrupts the spatial pattern of sensory bristles. Transfer of homozygous mutant animals to the restrictive temperature at the time of pupariation resulted in the elimination of sensory microchaetae and macrochaetae. This effect was specific to the sensory bristles; nonsensory bristles were not eliminated, nor were other types of innervated cuticular sense organs. In the case of the dorsal thoracic macrochaetae, normal ecd gene function is required during an early period of bristle development (0–18 h after puparium formation at 20 degrees C). It is during this period that important determinative events take place in developing imaginal tissues that are responsible for the establishment of bristle progenitor cells. It is proposed that the ecd gene product may be required for the response of certain classes of cells to specific, regulatory signals.

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