ZFIN ID: ZDB-PUB-160207-6
Feedback from each retinal neuron population drives expression of subsequent fate determinant genes without influencing the cell cycle exit timing
Ng Chi Kei, J., Dudczig, S., Currie, P.D., Jusuf, P.R.
Date: 2016
Source: The Journal of comparative neurology   524(13): 2553-66 (Journal)
Registered Authors: Currie, Peter D., Dudczig, Stefanie, Jusuf, Patricia
Keywords: RRID: AB_233622, RRID:ZIRC_ZL84, competence progression, histogenic birthorder, neurogenesis, zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Cycle/physiology*
  • Cell Differentiation/physiology
  • Feedback, Physiological/physiology*
  • Gene Expression Regulation, Developmental*
  • Neurogenesis/physiology*
  • Retina/embryology
  • Retina/physiology*
  • Retinal Neurons/physiology*
  • Time Factors
  • Zebrafish
PubMed: 26850379 Full text @ J. Comp. Neurol.
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.