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.

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 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 A local insulin reservoir ensures developmental progression in condition of nutrient shortage in Drosophila

2021 ◽  
Author(s):  
Suhrid Ghosh ◽  
Weihua Leng ◽  
Michaela Wilsch-Brauninger ◽  
Pierre Leopold ◽  
Suzanne Eaton
Keyword(s):  
Steroid Hormone ◽  
Neurosecretory Cells ◽  
Alpha Cell ◽  
Prothoracic Gland ◽  
Pupal Development ◽  
Corpora Cardiaca ◽  
Developmental Progression ◽  
Food Conditions ◽  
And Storage ◽  
Early Developmental

Insulin/IGF signalling (IIS) controls many aspects of development and physiology. In Drosophila, a conserved family of insulin-like peptides (Ilp) is produced by brain neurosecretory cells and exerts systemic functions. Here, we describe the local uptake and storage of Ilps in the Corpora Cardiaca (CC), a group of alpha cell homolog that produces the glucagon-like hormone AKH. Dilp uptake relies on the expression of Impl2, an IGF-BP that accumulates in the CCs. During nutrient shortage, this specific reserve of Ilps is released and activates IIS in a paracrine manner in the prothoracic gland, securing accelerated entry into pupal development through the production of the steroid hormone ecdysone. We therefore uncover a sparing mechanism whereby local Ilp storage and release activates the production of steroids and ensures early developmental progression in adverse food conditions.

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.

ADRENOCORTICAL FUNCTION IN PATIENTS WITH ACUTE SEVERE BRAIN AND PITUITARY LESION

1962 ◽  
Vol 40 (2) ◽  
pp. 254-262 ◽  
Author(s):  
H. H. Bassøe ◽  
R. Emberland ◽  
E. Glück ◽  
K. F. Støa
Keyword(s):  
Pituitary Gland ◽  
Adrenal Cortex ◽  
Artificial Ventilation ◽  
Practical Significance ◽  
Adrenocortical Function ◽  
The Third ◽  
Low Levels ◽  
Pituitary Lesion ◽  
Steroid Excretion ◽  
The Brain

ABSTRACT The steroid excretion and the plasma corticosteroids were investigated in three patients with necrosis of the brain and of the pituitary gland. The patients were kept alive by artificial ventilation. In two of the patients the neutral 17-ketosteroids and the 17-hydrocorticosteroids fell to extremely low levels. At the same time, the number of eosinophil cells showed a tendency to increase. Corticotrophin administered intravenously twice to the third patient had a stimulating effect on the adrenal cortex. The theoretical and practical significance of these findings is discussed.

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

The Meditations

2017 ◽  
Author(s):  
Walter Ott
Keyword(s):  
Perceptual Experience ◽  
Developmental Reading ◽  
Basic Structure ◽  
Brain Image ◽  
The Real ◽  
The Third ◽  
Real Work ◽  
Sensible Qualities ◽  
The Brain

Despite its difference in aspiration, the Meditations preserves the basic structure of perceptual experience outlined in Descartes’s earliest works. The chapter explores Descartes’s notion of an idea and uses a developmental reading to clear up the mystery surrounding material falsity. In the third Meditation, our protagonist does not yet know enough about extension in order to be able to tell whether her idea of cold is an idea of a real feature of bodies or merely the idea of a sensation. By the time she reaches the end of her reflections, she has learned that sensible qualities are at most sensations. As in his earliest stages, Descartes believes that the real work of perceiving the geometrical qualities of bodies is done by the brain image, which he persists in calling an ‘idea,’ at least when it is the object of mental awareness.

The effect of hypophysectomy on physiological color change in Fundulus heteroclitus

1971 ◽  
Vol 49 (1) ◽  
pp. 129-131 ◽  
Author(s):  
F. S. Abbott ◽  
M. B. Favreau
Keyword(s):  
Histological Examination ◽  
Fundulus Heteroclitus ◽  
Color Change ◽  
The Third ◽  
The Brain

Thirty-eight Fundulus heteroclitus were tested for ability to adapt to white and black backgrounds. They were then hypophysectomized and distributed individually to white and black containers. Their ability to adapt to background was determined for periods up to 2 weeks. Sixteen operated fish retained their preoperative ability to adapt; 8 became dark temporarily; 14 became persistently dark. Histological examination confirmed the result of the operation. In the third group of fish the persistent darkness was not associated with damage to specific areas of the brain although damage was more widespread in this group. It is concluded that hypophysectomy does not interfere with physiological color change in F. heteroclitus. The location of the central relays in the melanophore system could not be determined.

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