beta-Catenin Regulates Intercellular Signalling Networks and Cell-Type Specific Transcription in the Developing Mouse Midbrain-Rhombomere 1 Region
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Abstractb-catenin is a multifunctional protein involved in both signalling by secreted factors of Wnt family and regulation of the cellular architecture. We show that b-catenin stabilization in mouse midbrain-rhombomere1 region leads to robust upregulation of several Wnt signalling target genes, including Fgf8. Suggestive of direct transcriptional regulation of the Fgf8 gene, b-catenin stabilization resulted in Fgf8 up-regulation also in other tissues, specifically in the ventral limb ectoderm. Interestingly, stabilization of b-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 anteriorposterior and dorso-ventral patterning. The transcriptional regulatory functions of b-catenin were confirmed by b-catenin loss-of-function experiments. Temporally controlled inactivation of b-catenin revealed a cell-autonomous role for b-catenin in the maintenance of cell-type specific gene expression in the progenitors of midbrain dopaminergic neurons. These results highlight the role of b-catenin in establishment of neuroectodermal signalling centers, promoting region-specific gene expression and regulation of cell fate determination.
CitationPLoS One. 2010 Jun 3; 5(6):e10881
- Evidence that FGF8 signalling from the midbrain-hindbrain junction regulates growth and polarity in the developing midbrain.
- Authors: Lee SM, Danielian PS, Fritzsch B, McMahon AP
- Issue date: 1997 Mar
- Beta-catenin-mediated signaling and cell adhesion in postgastrulation mouse embryos.
- Authors: Hierholzer A, Kemler R
- Issue date: 2010 Jan
- Differential display of genes expressed at the midbrain - hindbrain junction identifies sprouty2: an FGF8-inducible member of a family of intracellular FGF antagonists.
- Authors: Chambers D, Medhurst AD, Walsh FS, Price J, Mason I
- Issue date: 2000 Jan
- Multiple roles of mesenchymal beta-catenin during murine limb patterning.
- Authors: Hill TP, Taketo MM, Birchmeier W, Hartmann C
- Issue date: 2006 Apr
- Bmp and Wnt/beta-catenin signals control expression of the transcription factor Olig3 and the specification of spinal cord neurons.
- Authors: Zechner D, Müller T, Wende H, Walther I, Taketo MM, Crenshaw EB 3rd, Treier M, Birchmeier W, Birchmeier C
- Issue date: 2007 Mar 1
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