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.
Highlights
The neocortex in mouse is formed during midembryogenesis in the prosencephalon as a multi-layer structure from cortical progenitors cells [1]
Tcf7L1 was strongly expressed in the lateral neocortical ventricular zone (VZ) and the signal declined in the medial wall and the hem (Fig. 1b, h)
We detected a clear presence of Tcf7L2 protein in the VZ of the neocortex and ganglionic eminences (GE) by immunohistochemistry on sections which was not previously indicated by in situ hybridization (Fig. 1c, k)
Summary
The neocortex in mouse is formed during midembryogenesis in the prosencephalon as a multi-layer structure from cortical progenitors cells [1]. Neural progenitor cells in the cortical ventricular zone (VZ) termed radial glial cells (RGC) generate neurons directly during asymmetric mode of cell division giving rise to one progenitor daughter cell and one daughter neuron, or one intermediate progenitor cell (IPC). IPCs may undergo few rounds of cell division in the subventricular zone (SVZ) before terminal differentiation into postmitotic neurons [2,3,4]. In the early forebrain at embryonic stages (E) 8-11 days post coitum, neural progenitors divide symmetrically to rapidly expand the progenitor pool before the asymmetric mode of cell division is initiated [5]. At E8-11, canonical Wnt/β-catenin signalling promotes symmetric division in the forebrain [6,7,8] while later (from E12.5 onwards)
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