Dual requirement for Pax6 in retinal progenitor cells.
Throughout the developing central nervous system, pre-patterning of the ventricular zone into discrete neural progenitor domains is one of the predominant strategies used to produce neuronal diversity in a spatially coordinated manner. In the retina, neurogenesis proceeds in an intricate chronological and spatial sequence, yet it remains unclear whether retinal progenitor cells (RPCs) display intrinsic heterogeneity at any given time point. Here, we performed a detailed study of RPC fate upon temporally and spatially confined inactivation of Pax6. Timed genetic removal of Pax6 appeared to unmask a cryptic divergence of RPCs into qualitatively divergent progenitor pools. In the more peripheral RPCs under normal circumstances, Pax6 seemed to prevent premature activation of a photoreceptor-differentiation pathway by suppressing expression of the transcription factor Crx. More centrally, Pax6 contributed to the execution of the comprehensive potential of RPCs: Pax6 ablation resulted in the exclusive generation of amacrine interneurons. Together, these data suggest an intricate dual role for Pax6 in retinal neurogenesis, while pointing to the cryptic divergence of RPCs into distinct progenitor pools.
Oron-Karni
Varda
V
Sackler Faculty of Medicine, Human Molecular Genetics and Biochemistry, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.
Farhy
Chen
C
Sackler Faculty of Medicine, Human Molecular Genetics and Biochemistry, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.
Elgart
Michael
M
Sackler Faculty of Medicine, Human Molecular Genetics and Biochemistry, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.
Marquardt
Till
T
European Neuroscience Institute, Developmental Neurobiology Laboratory, University of Göttingen Medical School/Max Planck Society, Grisebachstrasse 5, 37077 Göttingen, Germany.
Remizova
Lena
L
Sackler Faculty of Medicine, Human Molecular Genetics and Biochemistry, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.
Yaron
Orly
O
Sackler Faculty of Medicine, Human Molecular Genetics and Biochemistry, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.
Xie
Qing
Q
Albert Einstein College of Medicine, Departments of Ophthalmology and Visual Sciences and Genetics, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Cvekl
Ales
A
Albert Einstein College of Medicine, Departments of Ophthalmology and Visual Sciences and Genetics, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Ashery-Padan
Ruth
R
Sackler Faculty of Medicine, Human Molecular Genetics and Biochemistry, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000145:classification / Q000166:cytology; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009154:Mutation; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000196:embryology*; D055351:Retinal Neurons / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics
D017931:DNA Primers; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D015534:Trans-Activators; C109288:cone rod homeobox protein