Generation of neurons in the embryonic neocortex is a balanced process of proliferation and differentiation of neuronal progenitor cells. Canonical Wnt signalling is crucial for expansion of radial glial cells in the ventricular zone and for differentiation of intermediate progenitors in the subventricular zone. We detected abundant expression of two transcrtiption factors mediating canonical Wnt signalling, Tcf7L1 and Tcf7L2, in the ventricular zone of the embryonic neocortex. Conditional knock-out analysis showed that Tcf7L2, but not Tcf7L1, is the principal Wnt mediator important for maintenance of progenitor cell identity in the ventricular zone. In the absence of Tcf7L2, the Wnt activity is reduced, ventricular zone markers Pax6 and Sox2 are downregulated and the neuroepithelial structure is severed due to the loss of apical adherens junctions. This results in decreased proliferation of radial glial cells, the reduced number of intermediate progenitors in the subventricular zone and hypoplastic forebrain. Our data show that canonical Wnt signalling, which is essential for determining the neuroepithelial character of the neocortical ventricular zone, is mediated by Tcf7L2.

• Klíčová slova
• Neocortex, Neurogenenesis, Tcf7L1, Tcf7L2, Wnt signalling,
• MeSH
• buněčná diferenciace genetika   MeSH
• chlorid-hydrogenuhličitanové antiportéry MeSH
• down regulace genetika   MeSH
• embryo savčí MeSH
• hipokampus cytologie   embryologie   MeSH
• mutace genetika   MeSH
• myši transgenní MeSH
• myši MeSH
• neokortex cytologie   embryologie   MeSH
• nervové kmenové buňky fyziologie   MeSH
• neurogeneze fyziologie   MeSH
• neuroglie MeSH
• neurony fyziologie   MeSH
• počet buněk MeSH
• proliferace buněk genetika   MeSH
• protein 2 podobný transkripčnímu faktoru 7 genetika   metabolismus   MeSH
• proteiny T-boxu metabolismus   MeSH
• proteiny Wnt metabolismus   MeSH
• retinální gangliové buňky fyziologie   MeSH
• signální transdukce genetika   MeSH
• transkripční faktory SOXB1 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chlorid-hydrogenuhličitanové antiportéry MeSH
• Eomes protein, mouse MeSH Prohlížeč
• protein 2 podobný transkripčnímu faktoru 7 MeSH
• proteiny T-boxu MeSH
• proteiny Wnt MeSH
• Sox2 protein, mouse MeSH Prohlížeč
• Tcf7l2 protein, mouse MeSH Prohlížeč
• transkripční faktory SOXB1 MeSH

T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) proteins (TCFs) from the High Mobility Group (HMG) box family act as the main downstream effectors of the Wnt signaling pathway. The mammalian TCF/LEF family comprises four nuclear factors designated TCF7, LEF1, TCF7L1, and TCF7L2 (also known as TCF1, LEF1, TCF3, and TCF4, respectively). The proteins display common structural features and are often expressed in overlapping patterns implying their redundancy. Such redundancy was indeed observed in gene targeting studies; however, individual family members also exhibit unique features that are not recapitulated by the related proteins. In the present viewpoint, we summarized our current knowledge about the specific features of individual TCFs, namely structural-functional studies, posttranslational modifications, interacting partners, and phenotypes obtained upon gene targeting in the mouse. In addition, we employed several publicly available databases and web tools to evaluate the expression patterns and production of gene-specific isoforms of the TCF/LEF family members in human cells and tissues.

• Klíčová slova
• Fantom5, GTEx, Wnt signaling, splicing isoforms, the Cancer Genome Atlas,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH