Pax6 is required for delta-catenin/neurojugin expression during retinal, cerebellar and cortical development in mice.
The transcription factor Pax6 regulates multiple aspects of central nervous system (CNS) development. At the cellular level, the Pax6 mutation was reported to affect homophilic and heterophilic cellular adhesion, neuron polarity and neurite outgrowth. These abnormalities were observed in multiple regions of Pax6-mutant CNS, suggesting a common function for Pax6 in regulating cytoskeletal dynamics. However, target genes mediating Pax6 function in cytoskeletal dynamics remain largely unknown. Using DNA microarrays, we identified delta-catenin (delta-catenin /neurojugin) as a potential direct target of Pax6 in the CNS. delta-catenin encodes a large cytoskeletal protein that localizes at adherens junction in the CNS and that can modulate neurite outgrowth and N-cadherin turnover. delta-catenin was found to be co-expressed with Pax6 in several regions of the developing CNS. In Pax6 mutant embryos, delta-catenin expression was severely reduced in the optic vesicle neural ectoderm, in the ventricular zone of the neocortex and in the external granule layer of the cerebellum. We identified a Pax6 binding site in delta-catenin promoter that is conserved between mice and humans and which is effectively bound by Pax6 in vitro. Our results suggest that Pax6 regulates delta-catenin expression during CNS development in mice.
Duparc
Robert-Hugues
RH
Developmental Biology Laboratory, Maisonneuve-Rosemont Hospital, 5415 Boul. l'Assomption, Montreal, Canada, H1T 2M4.
Boutemmine
Djamila
D
Champagne
Marie-Pier
MP
Tétreault
Nicolas
N
Bernier
Gilbert
G
D000818:Animals; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D002531:Cerebellum / Q000196:embryology*; D002540:Cerebral Cortex / Q000196:embryology*; D005136:Eye Proteins / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D012097:Repressor Proteins / Q000502:physiology*; D012160:Retina / Q000196:embryology*; D000095002:Delta Catenin
D051177:Catenins; D015815:Cell Adhesion Molecules; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D010750:Phosphoproteins; D012097:Repressor Proteins; D000095002:Delta Catenin