Wnt/β-catenin signaling in cerebral cortical development

Abstract

The cerebral cortex is the center of our highest cognitive function, allowing the capacity for complex thought, language, and multiple other uniquely human characteristics. The mature cerebral cortex is organized in both the radial (inside to out) dimension into cortical layers as well as orthogonally into functional areas. In the radial dimension, cortical neurons reside in six functionally and morphologically distinct layers whose neurons differ in morphology, neurotransmitter use, and connectivity. In the orthogonal or tangential dimension, the cortex is also organized into functional areas that subserve distinct functions such as somatosensory, motor, visual, and higher association functions. Studies investigating the patterning of the cerebral cortex in this tangential dimension have revealed a complex interplay of discrete patterning centers serving to organize cell identity by the establishment of multiple opposing gradients of signaling molecules and transcription factors (Sur and Rubenstein, 2005). Relatively less is known about the molecules that pattern the cerebral cortex in the radial dimension. This review focuses on the role of the canonical Wnt/β-catenin signaling pathway in radial organization of the cerebral cortex.

Figures and Tables

Figure 1 Expression of Wnts, Frizzled and Wnt activity in the developing cerebral cortex. Neural precursor cells reside in the ventricular zone (VZ). Ventricular cells are polarized neuroepithelial cells oriented with their apical surfaces towards the ventricular lumen; the endfeet of ventricular zone neural precursors are joined by β-catenin-rich adherens junctions (red). Wnt7a, Fz-5 and Fz-8 are expressed in the cortical ventricular zone, while Wnt7b is expressed in the developing cortical plate. Active Wnt/β-catenin signaling is present in the ventricular zone and cortical plate (blue). Increasing evidence points to important Wnt function in proliferation of precursors, laminar fate determination of cortical neurons, axonal/dendritic remodeling, as well as synapse formation.

Table 1 CNS phenotype of Wnt knockouts