Abstract
β-catenin is a multifunctional protein involved in both signalling by secreted factors of Wnt family and regulation of the cellular architecture. We show that β-catenin stabilization in mouse midbrain-rhombomere1 region leads to robust up-regulation of several Wnt signalling target genes, including Fgf8. Suggestive of direct transcriptional regulation of the Fgf8 gene, β-catenin stabilization resulted in Fgf8 up-regulation also in other tissues, specifically in the ventral limb ectoderm. Interestingly, stabilization of β-catenin rapidly caused down-regulation of the expression of Wnt1 itself, suggesting a negative feedback loop. The changes in signal molecule expression were concomitant with deregulation of anterior-posterior and dorso-ventral patterning. The transcriptional regulatory functions of β-catenin were confirmed by β-catenin loss-of-function experiments. Temporally controlled inactivation of β-catenin revealed a cell-autonomous role for β-catenin in the maintenance of cell-type specific gene expression in the progenitors of midbrain dopaminergic neurons. These results highlight the role of β-catenin in establishment of neuroectodermal signalling centers, promoting region-specific gene expression and regulation of cell fate determination.
Highlights
Wnts are a family of secreted lipoproteins, which play a crucial role during embryogenesis via the regulation of patterning, cell fate decision and cell polarity
We have shown that b-catenin regulates anterior-posterior and dorso-ventral patterning in the midbrain-rhombomere 1 region at least partly by activating expression of Fgf8 and Shh, two other important patterning signals
Cross-talk between Wnt and Fgf8 signalling Accumulation of the degradation resistant b-catenin in the midbrain and rhombomere1 leads to drastic up-regulation of the expression of Wnt target genes, including Drapc1, Axin2 and Tcf1
Summary
Wnts are a family of secreted lipoproteins, which play a crucial role during embryogenesis via the regulation of patterning, cell fate decision and cell polarity. Wnts mediate their intracellular effects by inducing stabilization and nuclear translocation of bcatenin. In the absence of Wnt ligands, cytoplasmic b-catenin is phosphorylated by glycogen synthase kinase 3b (GSK3b). Phosphorylated b-catenin is targeted for ubiquitination and proteasomal degradation. Binding of Wnt molecules to their cell surface receptors releases b-catenin from the destruction complex followed by accumulation and nuclear translocation of b-catenin. Nuclear b-catenin complexes with the TCF/LEF family of transcription factors to regulate Wnt target gene expression (reviewed in [1])
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
