alphaE-catenin is not a significant regulator of beta-catenin signaling in the developing mammalian brain.
beta-Catenin is a crucial mediator of the canonical Wnt-signaling pathway. alpha-catenin is a major beta-catenin-binding protein, and overexpressed alpha-catenin can negatively regulate beta-catenin activity. Thus, alpha-catenin may be an important modulator of the Wnt pathway. We show here that endogenous alpha-catenin has little impact on the transcriptional activity of beta-catenin in developing mammalian organisms. We analyzed beta-catenin signaling in mice with conditional deletion of alphaE-catenin (Ctnna1) in the developing central nervous system. This mutation results in brain hyperplasia and we investigated whether activation of beta-catenin signaling may be at least partially responsible for this phenotype. To reveal potential quantitative or spatial changes in beta-catenin signaling, we used mice carrying a beta-catenin-signaling reporter transgene. In addition, we analyzed the expression of known endogenous targets of the beta-catenin pathway and the amount and localization of beta-catenin in mutant progenitor cells. We found that although loss of alphaE-catenin resulted in disruption of intercellular adhesion and hyperplasia in the developing brain, beta-catenin signaling was not altered. We conclude that endogenous alphaE-catenin has no significant impact on beta-catenin transcriptional activities in the developing mammalian brain.
Lien
Wen-Hui
WH
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Klezovitch
Olga
O
Null
Manda
M
Vasioukhin
Valeri
V
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D017930:Genes, Reporter; D006965:Hyperplasia; D008322:Mammals / Q000196:embryology*; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics; D051178:alpha Catenin / Q000172:deficiency / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D051820:TCF Transcription Factors; D051178:alpha Catenin; D051176:beta Catenin