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Insm1a-mediated gene repression is essential for the formation and differentiation of Müller glia-derived progenitors in the injured retina
by
Ramachandran, Rajesh
, Goldman, Daniel
, Zhao, Xiao-Feng
in
631/208/200
/ 631/378/1687
/ 631/378/2613/1786
/ 631/45/612/822
/ Animals
/ Basic Helix-Loop-Helix Transcription Factors - biosynthesis
/ Biomedical and Life Sciences
/ Cancer Research
/ Cell Biology
/ Cell differentiation
/ Cell Differentiation - physiology
/ Cell Proliferation
/ Developmental Biology
/ Gene expression
/ Gene Expression Regulation
/ Gene Silencing
/ Genes
/ Genetic aspects
/ Health aspects
/ Heparin-binding EGF-like Growth Factor
/ Intercellular Signaling Peptides and Proteins - biosynthesis
/ Life Sciences
/ MicroRNAs
/ Nerve Regeneration - genetics
/ Nerve Regeneration - physiology
/ Neural Stem Cells - physiology
/ Neuroglia
/ Neuroglia - physiology
/ Physiological aspects
/ Retina
/ Retina - cytology
/ Retina - injuries
/ Retina - physiology
/ Stem Cells
/ Transcription Factors - genetics
/ Transcription Factors - physiology
/ Zebrafish
/ Zebrafish - genetics
/ Zebrafish - physiology
/ Zebrafish Proteins - biosynthesis
/ Zebrafish Proteins - genetics
/ Zebrafish Proteins - physiology
2012
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Insm1a-mediated gene repression is essential for the formation and differentiation of Müller glia-derived progenitors in the injured retina
by
Ramachandran, Rajesh
, Goldman, Daniel
, Zhao, Xiao-Feng
in
631/208/200
/ 631/378/1687
/ 631/378/2613/1786
/ 631/45/612/822
/ Animals
/ Basic Helix-Loop-Helix Transcription Factors - biosynthesis
/ Biomedical and Life Sciences
/ Cancer Research
/ Cell Biology
/ Cell differentiation
/ Cell Differentiation - physiology
/ Cell Proliferation
/ Developmental Biology
/ Gene expression
/ Gene Expression Regulation
/ Gene Silencing
/ Genes
/ Genetic aspects
/ Health aspects
/ Heparin-binding EGF-like Growth Factor
/ Intercellular Signaling Peptides and Proteins - biosynthesis
/ Life Sciences
/ MicroRNAs
/ Nerve Regeneration - genetics
/ Nerve Regeneration - physiology
/ Neural Stem Cells - physiology
/ Neuroglia
/ Neuroglia - physiology
/ Physiological aspects
/ Retina
/ Retina - cytology
/ Retina - injuries
/ Retina - physiology
/ Stem Cells
/ Transcription Factors - genetics
/ Transcription Factors - physiology
/ Zebrafish
/ Zebrafish - genetics
/ Zebrafish - physiology
/ Zebrafish Proteins - biosynthesis
/ Zebrafish Proteins - genetics
/ Zebrafish Proteins - physiology
2012
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Insm1a-mediated gene repression is essential for the formation and differentiation of Müller glia-derived progenitors in the injured retina
by
Ramachandran, Rajesh
, Goldman, Daniel
, Zhao, Xiao-Feng
in
631/208/200
/ 631/378/1687
/ 631/378/2613/1786
/ 631/45/612/822
/ Animals
/ Basic Helix-Loop-Helix Transcription Factors - biosynthesis
/ Biomedical and Life Sciences
/ Cancer Research
/ Cell Biology
/ Cell differentiation
/ Cell Differentiation - physiology
/ Cell Proliferation
/ Developmental Biology
/ Gene expression
/ Gene Expression Regulation
/ Gene Silencing
/ Genes
/ Genetic aspects
/ Health aspects
/ Heparin-binding EGF-like Growth Factor
/ Intercellular Signaling Peptides and Proteins - biosynthesis
/ Life Sciences
/ MicroRNAs
/ Nerve Regeneration - genetics
/ Nerve Regeneration - physiology
/ Neural Stem Cells - physiology
/ Neuroglia
/ Neuroglia - physiology
/ Physiological aspects
/ Retina
/ Retina - cytology
/ Retina - injuries
/ Retina - physiology
/ Stem Cells
/ Transcription Factors - genetics
/ Transcription Factors - physiology
/ Zebrafish
/ Zebrafish - genetics
/ Zebrafish - physiology
/ Zebrafish Proteins - biosynthesis
/ Zebrafish Proteins - genetics
/ Zebrafish Proteins - physiology
2012
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Insm1a-mediated gene repression is essential for the formation and differentiation of Müller glia-derived progenitors in the injured retina
Journal Article
Insm1a-mediated gene repression is essential for the formation and differentiation of Müller glia-derived progenitors in the injured retina
2012
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Overview
In zebrafish, retinal injury stimulates Müller glia (MG) reprograming, allowing them to generate multipotent progenitors that replace damaged cells and restore vision. Recent studies suggest that transcriptional repression may underlie these events. To identify transcriptional repressors, we compared the transcriptomes of MG and MG-derived progenitors and identified
insm1a
, a repressor exhibiting a biphasic pattern of expression that is essential for retina regeneration. Insm1a was found to suppress
ascl1a
and its own expression, and link injury-dependent
ascl1a
induction with the suppression of the Wnt inhibitor
dickkopf
(
dkk
), which is necessary for MG dedifferentiation. We also found that Insm1a was responsible for sculpting the zone of injury-responsive MG by suppressing
h
b
-
e
g
f
a
expression. Finally, we provide evidence that Insm1a stimulates progenitor cell-cycle exit by suppressing a genetic program driving progenitor proliferation. Our studies identify Insm1a as a key regulator of retina regeneration and provide a mechanistic understanding of how it contributes to multiple phases of this process.
Goldman and colleagues report that the transcriptional repressor Insm1a is essential for retinal regeneration following injury in fish. Insm1a suppresses the expression of Ascl1a to promote Müller glial cells’ dedifferentiation at early stages of regeneration, and defines the regeneration zone by negatively regulating the expression of the heparin-binding EGF. It also halts the proliferation of retinal progenitors in the late stages of the process.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Basic Helix-Loop-Helix Transcription Factors - biosynthesis
/ Biomedical and Life Sciences
/ Cell Differentiation - physiology
/ Genes
/ Heparin-binding EGF-like Growth Factor
/ Intercellular Signaling Peptides and Proteins - biosynthesis
/ Nerve Regeneration - genetics
/ Nerve Regeneration - physiology
/ Neural Stem Cells - physiology
/ Retina
/ Transcription Factors - genetics
/ Transcription Factors - physiology
/ Zebrafish Proteins - biosynthesis
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