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De novo neurogenesis by targeted expression of atoh7 to Müller glia cells.

Lust K, Sinn R, Pérez Saturnino A, Centanin L, Wittbrodt J - Development (2016)

Bottom Line: The resulting neurogenic clusters differentiate in vivo into various retinal neurons.We use signaling reporters to demonstrate that the Atoh7-induced regeneration-like response of MG cells is mimicked by Notch, resembling the behavior of early progenitors during retinogenesis.Our results uncover a new role for Atoh7 as a universal neurogenic factor, and illustrate how signaling modules are re-employed in diverse contexts to trigger different biological responses.

View Article: PubMed Central - PubMed

Affiliation: Centre for Organismal Studies (COS) Heidelberg, Im Neuenheimer Feld 230, Heidelberg 69120, Germany The Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (HBIGS), Heidelberg University, Heidelberg, Germany.

No MeSH data available.


Related in: MedlinePlus

The LexPR system is suitablefor targetinggene expression to MG cells. (A-D″) The LexPR system allows targeted and inducible gene expression in medaka. In the uninduced state, the LexPR transactivator is retained in the cytoplasm, OP elements are inactive and genes of interest (G.o.I.) and fluorophores (FPs) are not expressed (A-B″). Upon induction, LexPR translocates into the nucleus and activates G.o.I. and FPs (C-D″). GFP expression (white/green) is only detected in induced fish in all different rx2 expression domains: the CMZ, the INL and the ONL. GFP-positive cells in the INL are also GS-positive (magenta) (D-D″, arrowheads). (E-H″) Targeted expression of atoh7 results in a transcriptionally active factor. atoh7::EGFP expression (white/green) is confined to RGCs in the central uninduced retina (F-F″). Upon induction, the targeted Atoh7 can activate its own promoter in GS-positive MG cells (magenta) leading to GFP expression (white/green) (G-H″, arrowheads). Scale bars: 20 µm.
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DEV135905F2: The LexPR system is suitablefor targetinggene expression to MG cells. (A-D″) The LexPR system allows targeted and inducible gene expression in medaka. In the uninduced state, the LexPR transactivator is retained in the cytoplasm, OP elements are inactive and genes of interest (G.o.I.) and fluorophores (FPs) are not expressed (A-B″). Upon induction, LexPR translocates into the nucleus and activates G.o.I. and FPs (C-D″). GFP expression (white/green) is only detected in induced fish in all different rx2 expression domains: the CMZ, the INL and the ONL. GFP-positive cells in the INL are also GS-positive (magenta) (D-D″, arrowheads). (E-H″) Targeted expression of atoh7 results in a transcriptionally active factor. atoh7::EGFP expression (white/green) is confined to RGCs in the central uninduced retina (F-F″). Upon induction, the targeted Atoh7 can activate its own promoter in GS-positive MG cells (magenta) leading to GFP expression (white/green) (G-H″, arrowheads). Scale bars: 20 µm.

Mentions: To address the role of Atoh7 in proliferation of MG cells, we used the LexPR inducible system (Emelyanov and Parinov, 2008) to trigger atoh7 expression in MG cells of the differentiated medaka retina. The LexPR system relies on the expression of a trans-activating element (LexPR), which only upon addition of mifepristone binds to one or more operator-promoter (OP) elements to drive gene expression (Emelyanov and Parinov, 2008) (see scheme in Fig. 2A,C). To drive expression of the LexPR to differentiated MG cells, we used the cis-regulatory element of rx2 (Martinez-Morales et al., 2009), which also targets photoreceptor cells and retinal stem cells in the CMZ (Inoue and Wittbrodt, 2011; Reinhardt et al., 2015).Fig. 2.


De novo neurogenesis by targeted expression of atoh7 to Müller glia cells.

Lust K, Sinn R, Pérez Saturnino A, Centanin L, Wittbrodt J - Development (2016)

The LexPR system is suitablefor targetinggene expression to MG cells. (A-D″) The LexPR system allows targeted and inducible gene expression in medaka. In the uninduced state, the LexPR transactivator is retained in the cytoplasm, OP elements are inactive and genes of interest (G.o.I.) and fluorophores (FPs) are not expressed (A-B″). Upon induction, LexPR translocates into the nucleus and activates G.o.I. and FPs (C-D″). GFP expression (white/green) is only detected in induced fish in all different rx2 expression domains: the CMZ, the INL and the ONL. GFP-positive cells in the INL are also GS-positive (magenta) (D-D″, arrowheads). (E-H″) Targeted expression of atoh7 results in a transcriptionally active factor. atoh7::EGFP expression (white/green) is confined to RGCs in the central uninduced retina (F-F″). Upon induction, the targeted Atoh7 can activate its own promoter in GS-positive MG cells (magenta) leading to GFP expression (white/green) (G-H″, arrowheads). Scale bars: 20 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920165&req=5

DEV135905F2: The LexPR system is suitablefor targetinggene expression to MG cells. (A-D″) The LexPR system allows targeted and inducible gene expression in medaka. In the uninduced state, the LexPR transactivator is retained in the cytoplasm, OP elements are inactive and genes of interest (G.o.I.) and fluorophores (FPs) are not expressed (A-B″). Upon induction, LexPR translocates into the nucleus and activates G.o.I. and FPs (C-D″). GFP expression (white/green) is only detected in induced fish in all different rx2 expression domains: the CMZ, the INL and the ONL. GFP-positive cells in the INL are also GS-positive (magenta) (D-D″, arrowheads). (E-H″) Targeted expression of atoh7 results in a transcriptionally active factor. atoh7::EGFP expression (white/green) is confined to RGCs in the central uninduced retina (F-F″). Upon induction, the targeted Atoh7 can activate its own promoter in GS-positive MG cells (magenta) leading to GFP expression (white/green) (G-H″, arrowheads). Scale bars: 20 µm.
Mentions: To address the role of Atoh7 in proliferation of MG cells, we used the LexPR inducible system (Emelyanov and Parinov, 2008) to trigger atoh7 expression in MG cells of the differentiated medaka retina. The LexPR system relies on the expression of a trans-activating element (LexPR), which only upon addition of mifepristone binds to one or more operator-promoter (OP) elements to drive gene expression (Emelyanov and Parinov, 2008) (see scheme in Fig. 2A,C). To drive expression of the LexPR to differentiated MG cells, we used the cis-regulatory element of rx2 (Martinez-Morales et al., 2009), which also targets photoreceptor cells and retinal stem cells in the CMZ (Inoue and Wittbrodt, 2011; Reinhardt et al., 2015).Fig. 2.

Bottom Line: The resulting neurogenic clusters differentiate in vivo into various retinal neurons.We use signaling reporters to demonstrate that the Atoh7-induced regeneration-like response of MG cells is mimicked by Notch, resembling the behavior of early progenitors during retinogenesis.Our results uncover a new role for Atoh7 as a universal neurogenic factor, and illustrate how signaling modules are re-employed in diverse contexts to trigger different biological responses.

View Article: PubMed Central - PubMed

Affiliation: Centre for Organismal Studies (COS) Heidelberg, Im Neuenheimer Feld 230, Heidelberg 69120, Germany The Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (HBIGS), Heidelberg University, Heidelberg, Germany.

No MeSH data available.


Related in: MedlinePlus