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ZIRC
ZFIN ID: ZDB-PUB-110221-17
Origin and determination of inhibitory cell lineages in the vertebrate retina
Jusuf, P.R., Almeida, A.D., Randlett, O., Joubin, K., Poggi, L., and Harris, W.A.
Date: 2011
Source: The Journal of neuroscience : the official journal of the Society for Neuroscience 31(7): 2549-2562 (Journal)
Registered Authors: Harris, William A., Joubin, Katherine, Jusuf, Patricia, Poggi, Lucia
Keywords: none
MeSH Terms:
  • Amacrine Cells/classification
  • Amacrine Cells/physiology
  • Animals
  • Animals, Genetically Modified
  • Blastomeres/transplantation
  • Bromodeoxyuridine/metabolism
  • Cell Differentiation/drug effects
  • Cell Differentiation/genetics*
  • Cell Lineage/genetics*
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Embryo, Nonmammalian
  • Embryonic Stem Cells/drug effects
  • Embryonic Stem Cells/physiology
  • Gene Expression Regulation, Developmental/genetics
  • Gene Expression Regulation, Developmental/physiology*
  • Glycine/metabolism
  • Green Fluorescent Proteins/genetics
  • Luminescent Proteins/genetics
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Neural Inhibition/genetics
  • Neural Inhibition/physiology*
  • Oligonucleotides, Antisense/pharmacology
  • Retina/cytology*
  • Retina/metabolism
  • Stem Cell Transplantation/methods
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • gamma-Aminobutyric Acid/metabolism
PubMed: 21325522 Full text @ J. Neurosci.
ABSTRACT
Multipotent progenitors in the vertebrate retina often generate clonally related mixtures of excitatory and inhibitory neurons. The postmitotically expressed transcription factor, Ptf1a, is essential for all inhibitory fates in the zebrafish retina, including three types of horizontal and 28 types of amacrine cell. Here, we show that specific types of inhibitory neurons arise from the cell-autonomous influence of Ptf1a in the daughters of fate-restricted progenitors, such as Ath5 or Vsx1/2-expressing progenitors, and that in the absence of Ptf1a, cells that would have become these specific inhibitory subtypes revert to the histogenetically appropriate excitatory subtypes of the same lineage. Altered proportions of amacrine subtypes respecified by the misexpression of Ptf1a in the Ath5 lineage suggest that Ath5-expressing progenitors are biased, favoring the generation of some subtypes more than others. Yet the full array of inhibitory cell subtypes in Ath5 mutants implies the existence of Ath5-independent factors involved in inhibitory cell specification. We also show that an extrinsic negative feedback on the expression of Ptf1a provides a control mechanism by which the number of any and all types of inhibitory cells in the retina can be regulated in this lineage-dependent way.
ADDITIONAL INFORMATION