Diverse Signaling by TGFβ Isoforms in Response to Focal Injury is Associated with Either Retinal Regeneration or Reactive Gliosis.

Conedera, Federica Maria; Quintela Pousa, Ana Maria; Presby, David Mikal; Mercader, Nadia; Enzmann, Volker; Tschopp, Markus (2021). Diverse Signaling by TGFβ Isoforms in Response to Focal Injury is Associated with Either Retinal Regeneration or Reactive Gliosis. Cellular and molecular neurobiology, 41(1), pp. 43-62. Springer 10.1007/s10571-020-00830-5

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Müller cells may have stem cell-like capability as they regenerate photoreceptor loss upon injury in some vertebrates, but not in mammals. Indeed, mammalian Müller cells undergo major cellular and molecular changes summarized as reactive gliosis. Transforming growth factor beta (TGFβ) isoforms are multifunctional cytokines that play a central role, both in wound healing and in tissue repair. Here, we studied the role of TGFβ isoforms and their signaling pathways in response to injury induction during tissue regeneration in zebrafish and scar formation in mouse. Our transcriptome analysis showed a different activation of canonical and non-canonical signaling pathways and how they shaped the injury response. In particular, TGFβ3 promotes retinal regeneration via Smad-dependent canonical pathway upon regulation of junb gene family and mycb in zebrafish Müller cells. However, in mice, TGFβ1 and TGFβ2 evoke the p38MAPK signaling pathway. The activation of this non-canonical pathway leads to retinal gliosis. Thus, the regenerative versus reparative effect of the TGFβ pathway observed may rely on the activation of different signaling cascades. This provides one explanation of the different injury response in zebrafish and mouse retina.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Augenklinik > Forschungsgruppe Augenheilkunde

UniBE Contributor:

Conedera, Federica Maria; Quintela Pousa, Ana Maria; Mercader Huber, Nadia Isabel and Enzmann, Volker

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0272-4340

Publisher:

Springer

Language:

English

Submitter:

Nadia Isabel Mercader Huber

Date Deposited:

10 Dec 2020 17:21

Last Modified:

01 Feb 2021 14:39

Publisher DOI:

10.1007/s10571-020-00830-5

PubMed ID:

32219603

Uncontrolled Keywords:

Laser injury Mouse Müller cell Reactive gliosis Retinal regeneration Tgfβ signaling Zebrafish

BORIS DOI:

10.7892/boris.147040

URI:

https://boris.unibe.ch/id/eprint/147040

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