Molecular Studies of Drosophila Signaling Pathways

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 3407

Special Issue Editor


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Guest Editor
Institute of Biology, Genetics Department 190g, University of Hohenheim, Stuttgart, Germany
Interests: Drosophila; Notch signaling; developmental genetics; transcriptional regulation; structure/function

Special Issue Information

Dear Colleagues,

Development is driven by just a handful of evolutionarily conserved signaling pathways including the Hedgehog (Hh), Wingless (Wg/Wnt), Decapentaplegic (Dpp)/Transforming Growth Factor-beta (TGFb), Notch and Receptor Tyrosine Kinase (RTK) pathways.

These pathways, together or individually, establish an animal’s body axes, coordinate pattern formation and orchestrate tissue morphogenesis. By controlling developmental cell-fate choices, they also determine the localization of specific cell types, i.e., the precise patterning of cell populations. Finally, they regulate cell proliferation, tissue growth and cell migration, as well as programmed cell death, to eventually shape tissues and organs. Defects in any of these pathways strongly affect human health, causing congenital diseases and cancer development. Hence, understanding the molecular details in signal transduction is of great medical interest as it may open avenues to therapeutic interventions.

Drosophila serves as a prime model for unveiling the molecular and biochemical mechanisms underlying the regulation of developmental signaling pathways. These include, amongst others, the many aspects of ligand and receptor activation, the identity of intracellular players and their regulation within the signaling cascade and, finally, the relaying of information to the genome and shaping of transcriptional responses.

This Special Issue aims to disseminate the most recent discoveries on the molecular basis of inter-cellular communication in Drosophila, with emphasis on their potential impact on human health, and will also address the newest techniques.

Dr. Anette Preiss
Guest Editor

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Keywords

  • regulation of signaling pathways
  • signal transduction mechanisms
  • signal dynamics
  • signaling networks and cross-talk
  • pathways and disease
  • cell-fate choices
  • developmental pattering
  • transcriptional regulation
  • computational modeling

Published Papers (4 papers)

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Research

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19 pages, 5669 KiB  
Article
Numerous Serine/Threonine Kinases Affect Blood Cell Homeostasis in Drosophila melanogaster
by Sebastian Deichsel, Bernd M. Gahr, Helena Mastel, Anette Preiss and Anja C. Nagel
Cells 2024, 13(7), 576; https://doi.org/10.3390/cells13070576 - 26 Mar 2024
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Abstract
Blood cells in Drosophila serve primarily innate immune responses. Various stressors influence blood cell homeostasis regarding both numbers and the proportion of blood cell types. The principle molecular mechanisms governing hematopoiesis are conserved amongst species and involve major signaling pathways like Notch, Toll, [...] Read more.
Blood cells in Drosophila serve primarily innate immune responses. Various stressors influence blood cell homeostasis regarding both numbers and the proportion of blood cell types. The principle molecular mechanisms governing hematopoiesis are conserved amongst species and involve major signaling pathways like Notch, Toll, JNK, JAK/Stat or RTK. Albeit signaling pathways generally rely on the activity of protein kinases, their specific contribution to hematopoiesis remains understudied. Here, we assess the role of Serine/Threonine kinases with the potential to phosphorylate the transcription factor Su(H) in crystal cell homeostasis. Su(H) is central to Notch signal transduction, and its inhibition by phosphorylation impedes crystal cell formation. Overall, nearly twenty percent of all Drosophila Serine/Threonine kinases were studied in two assays, global and hemocyte-specific overexpression and downregulation, respectively. Unexpectedly, the majority of kinases influenced crystal cell numbers, albeit only a few were related to hematopoiesis so far. Four kinases appeared essential for crystal cell formation, whereas most kinases restrained crystal cell development. This group comprises all kinase classes, indicative of the complex regulatory network underlying blood cell homeostasis. The rather indiscriminative response we observed opens the possibility that blood cells measure their overall phospho-status as a proxy for stress-signals, and activate an adaptive immune response accordingly. Full article
(This article belongs to the Special Issue Molecular Studies of Drosophila Signaling Pathways)
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21 pages, 5794 KiB  
Article
Separable Roles for Neur and Ubiquitin in Delta Signalling in the Drosophila CNS Lineages
by Konstantina Kalodimou, Margarita Stapountzi, Nicole Vüllings, Ekaterina Seib, Thomas Klein and Christos Delidakis
Cells 2023, 12(24), 2833; https://doi.org/10.3390/cells12242833 - 14 Dec 2023
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Abstract
The execution of a Notch signal at the plasma membrane relies on the mechanical force exerted onto Notch by its ligand. It has been appreciated that the DSL ligands need to collaborate with a ubiquitin (Ub) ligase, either Neuralized or Mindbomb1, in order [...] Read more.
The execution of a Notch signal at the plasma membrane relies on the mechanical force exerted onto Notch by its ligand. It has been appreciated that the DSL ligands need to collaborate with a ubiquitin (Ub) ligase, either Neuralized or Mindbomb1, in order to exert this pulling force, but the role of ubiquitylation per se is uncertain. Regarding the Delta–Neur pair, it is documented that neither the Neur catalytic domain nor the Delta intracellular lysines (putative Ub acceptors) are needed for activity. Here, we present a dissection of the Delta activity using the Delta–Notch-dependent expression of Hey in newborn Drosophila neurons as a sensitive in vivo assay. We show that the Delta–Neur interaction per se, rather than ubiquitylation, is needed for activity, pointing to the existence of a Delta–Neur signaling complex. The Neur catalytic domain, although not strictly needed, greatly improves Delta–Neur complex functionality when the Delta lysines are mutated, suggesting that the ubiquitylation of some component of the complex, other than Delta, can enhance signaling. Since Hey expression is sensitive to the perturbation of endocytosis, we propose that the Delta–Neur complex triggers a force-generating endocytosis event that activates Notch in the adjacent cell. Full article
(This article belongs to the Special Issue Molecular Studies of Drosophila Signaling Pathways)
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Review

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24 pages, 5437 KiB  
Review
Hedgehog on the Move: Glypican-Regulated Transport and Gradient Formation in Drosophila
by Carlos Jiménez-Jiménez, Kay Grobe and Isabel Guerrero
Cells 2024, 13(5), 418; https://doi.org/10.3390/cells13050418 - 27 Feb 2024
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Abstract
Glypicans (Glps) are a family of heparan sulphate proteoglycans that are attached to the outer plasma membrane leaflet of the producing cell by a glycosylphosphatidylinositol anchor. Glps are involved in the regulation of many signalling pathways, including those that regulate the activities of [...] Read more.
Glypicans (Glps) are a family of heparan sulphate proteoglycans that are attached to the outer plasma membrane leaflet of the producing cell by a glycosylphosphatidylinositol anchor. Glps are involved in the regulation of many signalling pathways, including those that regulate the activities of Wnts, Hedgehog (Hh), Fibroblast Growth Factors (FGFs), and Bone Morphogenetic Proteins (BMPs), among others. In the Hh-signalling pathway, Glps have been shown to be essential for ligand transport and the formation of Hh gradients over long distances, for the maintenance of Hh levels in the extracellular matrix, and for unimpaired ligand reception in distant recipient cells. Recently, two mechanistic models have been proposed to explain how Hh can form the signalling gradient and how Glps may contribute to it. In this review, we describe the structure, biochemistry, and metabolism of Glps and their interactions with different components of the Hh-signalling pathway that are important for the release, transport, and reception of Hh. Full article
(This article belongs to the Special Issue Molecular Studies of Drosophila Signaling Pathways)
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16 pages, 4420 KiB  
Review
Signaling Pathways Controlling Axonal Wrapping in Drosophila
by Marie Baldenius, Steffen Kautzmann, Suchet Nanda and Christian Klämbt
Cells 2023, 12(21), 2553; https://doi.org/10.3390/cells12212553 - 31 Oct 2023
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Abstract
The rapid transmission of action potentials is an important ability that enables efficient communication within the nervous system. Glial cells influence conduction velocity along axons by regulating the radial axonal diameter, providing electrical insulation as well as affecting the distribution of voltage-gated ion [...] Read more.
The rapid transmission of action potentials is an important ability that enables efficient communication within the nervous system. Glial cells influence conduction velocity along axons by regulating the radial axonal diameter, providing electrical insulation as well as affecting the distribution of voltage-gated ion channels. Differentiation of these wrapping glial cells requires a complex set of neuron–glia interactions involving three basic mechanistic features. The glia must recognize the axon, grow around it, and eventually arrest its growth to form single or multiple axon wraps. This likely depends on the integration of numerous evolutionary conserved signaling and adhesion systems. Here, we summarize the mechanisms and underlying signaling pathways that control glial wrapping in Drosophila and compare those to the mechanisms that control glial differentiation in mammals. This analysis shows that Drosophila is a beneficial model to study the development of even complex structures like myelin. Full article
(This article belongs to the Special Issue Molecular Studies of Drosophila Signaling Pathways)
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