Jusuf, P.R., Albadri, S., Paolini, A., Currie, P.D., Argenton, F., Higashijima, S., Harris, W.A., and Poggi, L. (2012) Biasing Amacrine Subtypes in the Atoh7 Lineage through Expression of Barhl2. The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(40):13929-13944.
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.