Tcf7L2 is essential for neurogenesis in the developing mouse neocortex

Abstract 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

Additional file 2: of Tcf7L2 is essential for neurogenesis in the developing mouse neocortex

Figure S2. Radial glial cells, cortical neurons and structure are not altered in in D6-Cre/Tcf7L1fl/fl/Tcf7L2fl/fl mutants at E15. a-c Hematoxylin-eosin staining of coronal sections from controls, Tcf7L2 single and Tcf7L1/Tcf7L2 double mutants. d-f Pax6 and Ctip2 double immunofluorescence with DAPI showing RGC marker Pax6. d‘-f‘Ctip2 immunofluorescence showing neuronal marker Ctip2 in the cortical plate (CP) at E15 in Tcf7L1/Tcf7L2 double mutants. g-i Tuj1 and Tbr2 double immunofluorescence counterstained with DAPI showing the cortical plate and intermediate neuronal progenitors in the SVZ at E15. g‘-i‘a higher magnification of Tbr2+ cells in the SVZ. . j-l PH3 and ZO1 double immunofluorescence with DAPI showing normal adherens junctions and normally dividing PH3+ progenitors at E15. j‘-l‘PH3 and ZO1 double immunofluorescence without DAPI. (JPG 2237 kb