Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina
| Autor: | Deepak A. Lamba, Joana Neves, Mia Koniikusic, Joshua Kramer, Heinrich Jasper |
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| Přispěvatelé: | Repositório da Universidade de Lisboa |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Photoreceptors
Cell signaling Sensory Receptors Social Sciences Apoptosis Stimulation Signal transduction chemistry.chemical_compound Transforming Growth Factor beta Animal Cells Medicine and Health Sciences Drosophila Proteins Psychology Neurons Multidisciplinary Cell Death Drosophila Melanogaster Signaling cascades Eukaryota Animal Models Cell biology Insects medicine.anatomical_structure Experimental Organism Systems Cell Processes DPP signaling cascade Medicine Drosophila Sensory Perception Anatomy Cellular Types Research Article Programmed cell death BMP signaling animal structures Arthropoda Science Ocular Anatomy Immune Cells Immunology Biology Research and Analysis Methods Bone morphogenetic protein Retina Model Organisms Ocular System medicine Animals Decapentaplegic Cognitive Psychology Organisms Biology and Life Sciences Afferent Neurons Retinal Cell Biology Invertebrates TGF-beta signaling cascade chemistry Cellular Neuroscience Animal Studies Cognitive Science Perception Receptors Transforming Growth Factor beta Zoology Entomology Homeostasis Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 16, Iss 10, p e0258872 (2021) Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP PLoS ONE, Vol 16, Iss 10 (2021) |
| Popis: | © 2021 Kramer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Retinal homeostasis relies on intricate coordination of cell death and survival in response to stress and damage. Signaling mechanisms that coordinate this process in the adult retina remain poorly understood. Here we identify Decapentaplegic (Dpp) signaling in Drosophila and its mammalian homologue Transforming Growth Factor-beta (TGFβ) superfamily, that includes TGFβ and Bone Morphogenetic Protein (BMP) signaling arms, as central mediators of retinal neuronal death and tissue survival following acute damage. Using a Drosophila model for UV-induced retinal damage, we show that Dpp released from immune cells promotes tissue loss after UV-induced retinal damage. Interestingly, we find a dynamic response of retinal cells to this signal: in an early phase, Dpp-mediated stimulation of Saxophone/Smox signaling promotes apoptosis, while at a later stage, stimulation of the Thickveins/Mad axis promotes tissue repair and survival. This dual role is conserved in the mammalian retina through the TGFβ/BMP signaling, as supplementation of BMP4 or inhibition of TGFβ using small molecules promotes retinal cell survival, while inhibition of BMP negatively affects cell survival after light-induced photoreceptor damage and NMDA induced inner retinal neuronal damage. Our data identify key evolutionarily conserved mechanisms by which retinal homeostasis is maintained. The research presented here is supported by NIH grants (R01 EY025779 and EY032197 to DL; AG057353 and EY018177 to HJ; P30 Vision Core grant to UCSF Dept of Ophthalmology), and the Research to Prevent Blindness (unrestricted grant to UCSF Dept of Ophthalmology). |
| Databáze: | OpenAIRE |
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