ZFIN ID: ZDB-PUB-121016-1
Biasing Amacrine Subtypes in the Atoh7 Lineage through Expression of Barhl2
Jusuf, P.R., Albadri, S., Paolini, A., Currie, P.D., Argenton, F., Higashijima, S., Harris, W.A., and Poggi, L.
Date: 2012
Source: The Journal of neuroscience : the official journal of the Society for Neuroscience   32(40): 13929-13944 (Journal)
Registered Authors: Albadri, Shahad, Argenton, Francesco, Currie, Peter D., Harris, William A., Higashijima, Shin-ichi, Jusuf, Patricia, Paolini, Alessio, Poggi, Lucia
Keywords: none
MeSH Terms:
  • Amacrine Cells/classification
  • Amacrine Cells/cytology*
  • Amacrine Cells/metabolism
  • Animals
  • Animals, Genetically Modified
  • Cell Division
  • Cell Lineage
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/physiology*
  • Female
  • Gene Expression Regulation, Developmental/drug effects
  • Helix-Loop-Helix Motifs/physiology
  • Male
  • Morpholinos/pharmacology
  • Retina/embryology
  • Time-Lapse Imaging
  • Transcription Factors/biosynthesis
  • Transcription Factors/genetics
  • Transcription Factors/physiology*
  • Transcription, Genetic/drug effects
  • Zebrafish
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 23035102 Full text @ J. Neurosci.

Within the developing vertebrate retina, particular subtypes of amacrine cells (ACs) tend to arise from progenitors expressing the basic helix-loop-helix (bHLH) transcription factor, Atoh7, which is necessary for the early generation of retinal ganglion cells (RGCs). All ACs require the postmitotic expression of the bHLH pancreas transcription factor Ptf1a; however, Ptf1a alone is not sufficient to give subtype identities. Here we use functional and in vivo time-lapse studies in the zebrafish retina to investigate on the developmental programs leading to ACs specification within the subsequent divisions of Atoh7-positive progenitors. We find evidences that the homeobox transcription factor Barhl2 is an AC subtype identity-biasing factor that turns on within Atoh7-positive descendants. In vivo lineage tracing reveals that particular modes of cell division tend to generate Barhl2-positive precursors from sisters of RGCs. Additionally, Atoh7 indirectly impacts these division modes to regulate the right number of barhl2-expressing cells. We finally find that Atoh7 itself influences the subtypes of Barhl2-dependent ACs. Together, the results from our study uncover lineage-related and molecular logic of subtype specification in the vertebrate retina, by showing that specific AC subtypes arise via a particular mode of cell division and a transcriptional network cascade involving the sequential expression of first atoh7 followed by ptf1a and then barhl2.