Feedback from each retinal neuron population drives expression of subsequent fate determinant genes without influencing the cell cycle exit timing

Jeremy Ng Chi Kei, Stefanie Dudczig, Peter D Currie, Patricia Regina Jusuf

Research output: Contribution to journalArticleResearchpeer-review

Abstract

During neurogenesis progenitors balance proliferation and cell cycle exit together with expression of fate determinant genes to ensure that the correct number of each of these neuron types is generated. While intrinsic gene expression acting cell-autonomously within each progenitor drives these processes, the final number of neurons generated is also influenced by extrinsic cues, which represents a potential avenue to direct neurogenesis in developmental disorders or regenerative settings without the need to change intrinsic gene expression. Thus it is important to understand which of these stages of neurogenesis are amenable to such extrinsic influences. Additionally, all types of neurons are specified in a highly conserved histogenic order, though its significance is unknown. Here, we make use of conserved patterns of neurogenesis in the relatively simple, yet highly organised zebrafish retina model, in which such histogenic birthorder is well characterised. We directly visualised and quantified birthdates and cell fate determinant expression in wild type vs environments lacking different neuronal populations. Our work shows that extrinsic feedback from developing retinal neurons is important for the temporal expression of intrinsic fate determinants but not the timing of birthdates. We found no changes in cell cycle exit timing, but a significant delay in the expression of genes driving the generation only of later, but not earlier born cells, suggesting that the robustness of this process depends on continuous feedback from earlier formed cell types. Thus, extrinsic cues selectively influence cell fate determinant progression which may explain the function of the observed retinal histogenic order. This article is protected by copyright. All rights reserved.
Original languageEnglish
Pages (from-to)2553-2566
Number of pages14
JournalJournal of Comparative Neurology
Volume524
Issue number13
DOIs
Publication statusPublished - 2016

Cite this

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title = "Feedback from each retinal neuron population drives expression of subsequent fate determinant genes without influencing the cell cycle exit timing",
abstract = "During neurogenesis progenitors balance proliferation and cell cycle exit together with expression of fate determinant genes to ensure that the correct number of each of these neuron types is generated. While intrinsic gene expression acting cell-autonomously within each progenitor drives these processes, the final number of neurons generated is also influenced by extrinsic cues, which represents a potential avenue to direct neurogenesis in developmental disorders or regenerative settings without the need to change intrinsic gene expression. Thus it is important to understand which of these stages of neurogenesis are amenable to such extrinsic influences. Additionally, all types of neurons are specified in a highly conserved histogenic order, though its significance is unknown. Here, we make use of conserved patterns of neurogenesis in the relatively simple, yet highly organised zebrafish retina model, in which such histogenic birthorder is well characterised. We directly visualised and quantified birthdates and cell fate determinant expression in wild type vs environments lacking different neuronal populations. Our work shows that extrinsic feedback from developing retinal neurons is important for the temporal expression of intrinsic fate determinants but not the timing of birthdates. We found no changes in cell cycle exit timing, but a significant delay in the expression of genes driving the generation only of later, but not earlier born cells, suggesting that the robustness of this process depends on continuous feedback from earlier formed cell types. Thus, extrinsic cues selectively influence cell fate determinant progression which may explain the function of the observed retinal histogenic order. This article is protected by copyright. All rights reserved.",
author = "{Chi Kei}, {Jeremy Ng} and Stefanie Dudczig and Currie, {Peter D} and Jusuf, {Patricia Regina}",
year = "2016",
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pages = "2553--2566",
journal = "Journal of Comparative Neurology",
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}

Feedback from each retinal neuron population drives expression of subsequent fate determinant genes without influencing the cell cycle exit timing. / Chi Kei, Jeremy Ng; Dudczig, Stefanie; Currie, Peter D; Jusuf, Patricia Regina.

In: Journal of Comparative Neurology, Vol. 524, No. 13, 2016, p. 2553-2566.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Dudczig, Stefanie

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N2 - During neurogenesis progenitors balance proliferation and cell cycle exit together with expression of fate determinant genes to ensure that the correct number of each of these neuron types is generated. While intrinsic gene expression acting cell-autonomously within each progenitor drives these processes, the final number of neurons generated is also influenced by extrinsic cues, which represents a potential avenue to direct neurogenesis in developmental disorders or regenerative settings without the need to change intrinsic gene expression. Thus it is important to understand which of these stages of neurogenesis are amenable to such extrinsic influences. Additionally, all types of neurons are specified in a highly conserved histogenic order, though its significance is unknown. Here, we make use of conserved patterns of neurogenesis in the relatively simple, yet highly organised zebrafish retina model, in which such histogenic birthorder is well characterised. We directly visualised and quantified birthdates and cell fate determinant expression in wild type vs environments lacking different neuronal populations. Our work shows that extrinsic feedback from developing retinal neurons is important for the temporal expression of intrinsic fate determinants but not the timing of birthdates. We found no changes in cell cycle exit timing, but a significant delay in the expression of genes driving the generation only of later, but not earlier born cells, suggesting that the robustness of this process depends on continuous feedback from earlier formed cell types. Thus, extrinsic cues selectively influence cell fate determinant progression which may explain the function of the observed retinal histogenic order. This article is protected by copyright. All rights reserved.

AB - During neurogenesis progenitors balance proliferation and cell cycle exit together with expression of fate determinant genes to ensure that the correct number of each of these neuron types is generated. While intrinsic gene expression acting cell-autonomously within each progenitor drives these processes, the final number of neurons generated is also influenced by extrinsic cues, which represents a potential avenue to direct neurogenesis in developmental disorders or regenerative settings without the need to change intrinsic gene expression. Thus it is important to understand which of these stages of neurogenesis are amenable to such extrinsic influences. Additionally, all types of neurons are specified in a highly conserved histogenic order, though its significance is unknown. Here, we make use of conserved patterns of neurogenesis in the relatively simple, yet highly organised zebrafish retina model, in which such histogenic birthorder is well characterised. We directly visualised and quantified birthdates and cell fate determinant expression in wild type vs environments lacking different neuronal populations. Our work shows that extrinsic feedback from developing retinal neurons is important for the temporal expression of intrinsic fate determinants but not the timing of birthdates. We found no changes in cell cycle exit timing, but a significant delay in the expression of genes driving the generation only of later, but not earlier born cells, suggesting that the robustness of this process depends on continuous feedback from earlier formed cell types. Thus, extrinsic cues selectively influence cell fate determinant progression which may explain the function of the observed retinal histogenic order. This article is protected by copyright. All rights reserved.

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