Hedgehog signaling can enhance glycolytic
            <scp>ATP</scp>
            production in the
            <i>Drosophila</i>
            wing disc

Nellas, Ioannis; Iyer, K. Venkatesan; Iglesias-Artola, Juan M.; Pippel, Martin; Nadler, André; Eaton, Suzanne; Dye, Natalie A.

doi:10.15252/embr.202154025

Cited by 6 publications

(7 citation statements)

References 46 publications

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“…Recent data associates intercellular signaling to energy metabolism processes during tissue growth of embryonic systems [28][29][30][31]. In this sense, we explored potential metabolic alterations induced by RA signaling stimulation versus inhibition.…”

Section: Retinoic Acid Signaling Stimulation Requires Less Glucose Co...mentioning

confidence: 99%

“…In this model, the expression of glucose catabolism genes is regulated by Notch signaling, and this mechanism is proposed to promote the growth of this developing tissue [28]. Moreover, it was recently described that the Hedgehog signaling pathway can enhance glycolytic ATP production in Drosophila wing discs [29]. In a different study, during Zebra sh neural tissue development, Notch signaling was described to regulate the expression of glycolysis-related genes in a stage-speci c manner [30].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Retinoic acid signaling regulates the energy metabolism of embryonic lung branching

Fernandes-Silva¹,

Alves²,

Garcez³

et al. 2023

Preprint

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Background: Lung branching morphogenesis is characterized by epithelial-mesenchymal interactions and mediated by complex signaling that ultimately defines the airway conducting system. Retinoic Acid (RA) signaling is crucial for lung organogenesis and modulates proximal-distal patterning and branching morphogenesis. However, how signaling networks and energy metabolism work together to shape embryonic lung development remains unexplored. Here, we investigate how RA signaling influences the metabolic profile of lung branching. Methods: We performed ex vivo lung explant culture using embryonic chicken lungs (Gallus gallus) treated with DMSO, 1 uM RA (stimulation), or 10 uM of BMS493 (inhibition). Explant culture media was collected, and the consumption/production of extracellular metabolites was evaluated by 1H-NMR spectroscopy. Lung explants were analyzed to determine mitochondrial respiration and biogenesis. Proliferation was assessed using an EdU‐based assay. Western blot, qPCR, and in situ hybridization were performed to assess the expression of metabolic/signaling components. Results: Upon stimulation, RA signaling increases lung branching, maintaining proper morphology. Besides, there is an increase in the amount of glucose directed into pyruvate and succinate rather than into alanine or lactate production. On the other hand, RA signaling inhibition decreases lung branching, induces a cystic-like phenotype, and promotes mitochondrial function. Proliferation status and lactate dehydrogenase expression are both regulated by RA signaling. Furthermore, RA signaling controls fatty acid metabolism through an AMPK-dependent mechanism. Conclusions: This report shows that RA signaling modulates the energy metabolism of lung branching morphogenesis and highlights the importance of metabolic regulation in this phase, contributing to understanding the etiology of congenital lung disorders.

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Section: Retinoic Acid Signaling Stimulation Requires Less Glucose Co...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Retinoic acid signaling regulates the energy metabolism of embryonic lung branching

Fernandes-Silva¹,

Alves²,

Garcez³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Conversely, the absence of Notch signaling leads to a decrease in glycolytic gene expression [28]. The Hedgehog signaling pathway can enhance glycolytic ATP production in Drosophila wing discs [29]. During Zebrafish neural tissue development, Notch signaling regulates the expression of glycolysisrelated genes in a stage-specific manner [30].…”

Section: Introductionmentioning

confidence: 99%

Retinoic Acid-mediated control of energy metabolism is essential for lung branching morphogenesis

Fernandes-Silva,

Alves,

Garcez

et al. 2024

Preprint

View full text Add to dashboard Cite

Lung branching morphogenesis relies on intricate epithelial-mesenchymal interactions and signaling networks. Still, the interplay between signaling and energy metabolism in shaping embryonic lung development remains unexplored. Retinoic Acid (RA) signaling influences lung proximal-distal patterning and branching morphogenesis, but its role as metabolic modulator is unknown. Hence, this study investigates how RA signaling affects the metabolic profile of lung branching. We performed ex vivo lung explant culture of embryonic chicken lungs treated with DMSO, 1 µM RA, or 10 µM BMS493. Extracellular metabolite consumption/production was evaluated by 1H-NMR spectroscopy. Mitochondrial respiration and biogenesis were also analyzed. Proliferation was assessed using an EdU-based assay. The expression of crucial metabolic/signaling components was examined through western blot, qPCR, and in situ hybridization. RA signaling stimulation redirects glucose towards pyruvate and succinate production rather than to alanine or lactate. Inhibition of RA signaling reduces lung branching, resulting in a cystic-like phenotype while promoting mitochondrial function. Here, RA signaling emerges as a regulator of tissue proliferation and lactate dehydrogenase expression. Furthermore, RA governs fatty acid metabolism through an AMPK-dependent mechanism. These findings underscore RA's pivotal role in shaping lung metabolism during branching morphogenesis, contributing to our understanding of lung development and cystic-related lung disorders.

show abstract

“…Conversely, absence of Notch signaling leads to a decrease in glycolytic gene expression [28]. The Hedgehog signaling pathway can enhance glycolytic ATP production in Drosophila wing discs [29]. During neural tissue development in Zebrafish, Notch signaling regulates the expression of glycolysis-related genes in a stage-specific manner [30].…”

Section: Introductionmentioning

confidence: 99%

Retinoic Acid-Mediated Control of Energy Metabolism Is Essential for Lung Branching Morphogenesis

Fernandes-Silva,

Alves,

Garcez

et al. 2024

IJMS

View full text Add to dashboard Cite

Lung branching morphogenesis relies on intricate epithelial–mesenchymal interactions and signaling networks. Still, the interplay between signaling and energy metabolism in shaping embryonic lung development remains unexplored. Retinoic acid (RA) signaling influences lung proximal–distal patterning and branching morphogenesis, but its role as a metabolic modulator is unknown. Hence, this study investigates how RA signaling affects the metabolic profile of lung branching. We performed ex vivo lung explant culture of embryonic chicken lungs treated with DMSO, 1 µM RA, or 10 µM BMS493. Extracellular metabolite consumption/production was evaluated by using 1H-NMR spectroscopy. Mitochondrial respiration and biogenesis were also analyzed. Proliferation was assessed using an EdU-based assay. The expression of crucial metabolic/signaling components was examined through Western blot, qPCR, and in situ hybridization. RA signaling stimulation redirects glucose towards pyruvate and succinate production rather than to alanine or lactate. Inhibition of RA signaling reduces lung branching, resulting in a cystic-like phenotype while promoting mitochondrial function. Here, RA signaling emerges as a regulator of tissue proliferation and lactate dehydrogenase expression. Furthermore, RA governs fatty acid metabolism through an AMPK-dependent mechanism. These findings underscore RA’s pivotal role in shaping lung metabolism during branching morphogenesis, contributing to our understanding of lung development and cystic-related lung disorders.

show abstract

Hedgehog signaling can enhance glycolytic ATP production in the Drosophila wing disc

Cited by 6 publications

References 46 publications

Retinoic acid signaling regulates the energy metabolism of embryonic lung branching

Retinoic acid signaling regulates the energy metabolism of embryonic lung branching

Retinoic Acid-mediated control of energy metabolism is essential for lung branching morphogenesis

Retinoic Acid-Mediated Control of Energy Metabolism Is Essential for Lung Branching Morphogenesis

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