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.

Institute of Molecular Genetics of the Czech Academy of Sciences Vídeňská 1084 14200 Prague Czech Republic

Institute of Molecular Genetics of the Czech Academy of Sciences Vídeňská 1084 14200 Prague Czech Republic Institute of Experimental Medicine of the Czech Academy of Sciences Vídeňská 1084 14200 Prague Czech Republic

Institute of Molecular Genetics of the Czech Academy of Sciences Vídeňská 1084 14200 Prague Czech Republic Laboratory of Eye Biology Division BIOCEV Institute of Molecular Genetics of the Czech Academy of Sciences Prumyslova 595 Vestec Czech Republic

Institute of Molecular Genetics of the Czech Academy of Sciences Vídeňská 1084 14200 Prague Czech Republic Present address Department of Biosciences and Nutrition Karolinska Institutet SE 14183 Huddinge Sweden

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