Abstract:
:The Wnt/β-catenin signaling pathway plays crucial roles in early hindbrain formation, and its constitutive activity is associated with a subset of human medulloblastoma, a malignant childhood tumor of the posterior fossa. However, the precise function of Wnt/β-catenin signaling during cerebellar development is still elusive. We generated Math1-cre::Apc(Fl/Fl) mice with a conditional knockout for the Adenomatosis polyposis coli (Apc) gene that displayed a constitutive activity of Wnt/β-catenin signaling in cerebellar granule neuron precursors. Such mice showed normal survival without any tumor formation but had a significantly smaller cerebellum with a complete disruption of its cortical histoarchitecture. The activation of the Wnt/β-catenin signaling pathway resulted in a severely inhibited proliferation and premature differentiation of cerebellar granule neuron precursors in vitro and in vivo. Mutant mice hardly developed an internal granular layer, and layering of Purkinje neurons was disorganized. Clinically, these mice presented with significantly impaired motor coordination and ataxia. In summary, we conclude that cerebellar granule neurons essentially require appropriate levels of Wnt signaling to balance their proliferation and differentiation.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Lorenz A,Deutschmann M,Ahlfeld J,Prix C,Koch A,Smits R,Fodde R,Kretzschmar HA,Schüller Udoi
10.1128/MCB.05718-11subject
Has Abstractpub_date
2011-08-01 00:00:00pages
3326-38issue
16eissn
0270-7306issn
1098-5549pii
MCB.05718-11journal_volume
31pub_type
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