Pax6 is required for the multipotent state of retinal progenitor cells.
The molecular mechanisms mediating the retinogenic potential of multipotent retinal progenitor cells (RPCs) are poorly defined. Prior to initiating retinogenesis, RPCs express a limited set of transcription factors implicated in the evolutionary ancient genetic network that initiates eye development. We elucidated the function of one of these factors, Pax6, in the RPCs of the intact developing eye by conditional gene targeting. Upon Pax6 inactivation, the potential of RPCs becomes entirely restricted to only one of the cell fates normally available to RPCs, resulting in the exclusive generation of amacrine interneurons. Our findings demonstrate furthermore that Pax6 directly controls the transcriptional activation of retinogenic bHLH factors that bias subsets of RPCs toward the different retinal cell fates, thereby mediating the full retinogenic potential of RPCs.
Marquardt
T
T
Max-Planck-Institute of Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg 11, D-37077, Göttingen, Germany.
Ashery-Padan
R
R
Andrejewski
N
N
Scardigli
R
R
Guillemot
F
F
Gruss
P
P
D000818:Animals; D002460:Cell Line; D019070:Cell Lineage; D002642:Chick Embryo; D002999:Clone Cells / Q000166:cytology; D005136:Eye Proteins; D018390:Gene Targeting; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D018377:Neurotransmitter Agents / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D050765:Qa-SNARE Proteins; D012097:Repressor Proteins; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D005136:Eye Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D050765:Qa-SNARE Proteins; D012097:Repressor Proteins; D014157:Transcription Factors