Beta-catenin is essential for lamination but not neurogenesis in mouse retinal development.
During vertebrate retinal development, the seven retinal cell types differentiate sequentially from a single population of retinal progenitor cells (RPCs) and organize themselves into a distinct laminar structure. The purpose of this study was to determine whether beta-catenin, which functions both as a nuclear effector for the canonical Wnt signaling pathway and as a regulator of cell adhesion, is required for retinal neurogenesis or lamination. We used the Cre-loxP system to either eliminate beta-catenin or to express a constitutively active form during retinal neurogenesis. Eliminating beta-catenin did not affect cell differentiation, but did result in the loss of the radial arrangement of RPCs and caused abnormal migration of differentiated neurons. As a result, the laminar structure was massively disrupted in beta-catenin-null retinas, although all retinal cell types still formed. In contrast to other neural tissues, eliminating beta-catenin did not significantly reduce the proliferation rate of RPCs; likewise, activating beta-catenin ectopically in RPCs did not result in overproliferation, but loss of neural retinal identity. These results indicate that beta-catenin is essential during retinal neurogenesis as a regulator of cell adhesion but not as a nuclear effector of the canonical Wnt signaling pathway. The results further imply that retinal lamination and retinal cell differentiation are genetically separable processes.
Fu
Xueyao
X
Department of Biochemistry and Molecular Biology, Unit 1000, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Sun
Hongxia
H
Klein
William H
WH
Mu
Xiuqian
X
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*; D000099293:Protein Kinase C-lambda
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D007527:Isoenzymes; D011493:Protein Kinase C; D051153:Wnt Proteins; D051176:beta Catenin; D000099293:Protein Kinase C-lambda; C115084:Pard3 protein, mouse