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

• Published in: Cellular and molecular neurobiology Vol. 41; no. 1; pp. 43 - 62
• Main Authors: Conedera, Federica Maria, Quintela Pousa, Ana Maria, Presby, David Mikal, Mercader, Nadia, Enzmann, Volker, Tschopp, Markus
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2021; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell Biology; Cytokines; Danio rerio; Gene expression; Gliosis; Isoforms; JunB protein; Mammals; Neurobiology; Neurosciences; Original Research; Retina; Signal transduction; Smad protein; Stem cells; Transcriptomes; Transforming growth factor-b; Transforming growth factor-b1; Wound healing; Laser injury; Tgfβ signaling; Müller cell; Mouse; Reactive gliosis; Zebrafish; Retinal regeneration
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-020-00830-5

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.