Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina

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...

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Autores principales:	Joshua Kramer, Joana Neves, Mia Koniikusic, Heinrich Jasper, Deepak A. Lamba
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dd374bf7e91e48159136f70487efee7c
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spelling	oai:doaj.org-article:dd374bf7e91e48159136f70487efee7c2021-11-04T06:19:43ZDpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina1932-6203https://doaj.org/article/dd374bf7e91e48159136f70487efee7c2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547621/?tool=EBIhttps://doaj.org/toc/1932-6203Retinal 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.Joshua KramerJoana NevesMia KoniikusicHeinrich JasperDeepak A. LambaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joshua Kramer Joana Neves Mia Koniikusic Heinrich Jasper Deepak A. Lamba Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina
description	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.
format	article
author	Joshua Kramer Joana Neves Mia Koniikusic Heinrich Jasper Deepak A. Lamba
author_facet	Joshua Kramer Joana Neves Mia Koniikusic Heinrich Jasper Deepak A. Lamba
author_sort	Joshua Kramer
title	Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina
title_short	Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina
title_full	Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina
title_fullStr	Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina
title_full_unstemmed	Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina
title_sort	dpp/tgfβ-superfamily play a dual conserved role in mediating the damage response in the retina
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/dd374bf7e91e48159136f70487efee7c
work_keys_str_mv	AT joshuakramer dpptgfbsuperfamilyplayadualconservedroleinmediatingthedamageresponseintheretina AT joananeves dpptgfbsuperfamilyplayadualconservedroleinmediatingthedamageresponseintheretina AT miakoniikusic dpptgfbsuperfamilyplayadualconservedroleinmediatingthedamageresponseintheretina AT heinrichjasper dpptgfbsuperfamilyplayadualconservedroleinmediatingthedamageresponseintheretina AT deepakalamba dpptgfbsuperfamilyplayadualconservedroleinmediatingthedamageresponseintheretina
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Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina

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