β-catenin–mediated Wnt signaling regulates neurogenesis in the ventral telencephalon

Abstract

Genetic ablation of β-catenin in the embryonic ventral forebrain restricted proliferation of neural precursors in the medial ganglionic eminence, resulting in fewer cholinergic projection neurons in basal forebrain and fewer calbindin- and somatostatin-positive interneurons in the cortex. This work suggests a crucial role for canonical Wnt signaling in ventral forebrain neurogenesis. Development of the telencephalon involves the coordinated growth of diversely patterned brain structures. Previous studies have demonstrated the importance of β-catenin–mediated Wnt signaling in proliferation and fate determination during cerebral cortical development. We found that β-catenin–mediated Wnt signaling critically maintained progenitor proliferation in the subcortical (pallidal) telencephalon. Targeted deletion of β-catenin in mice severely impaired proliferation in the medial ganglionic eminence without grossly altering differentiated fate. Several lines of evidence suggest that this phenotype is primarily the result of a loss of canonical Wnt signaling. As previous studies have suggested that the ventral patterning factor Sonic Hedgehog (Shh) also stimulates dorsal telencephalic proliferation, we propose a model whereby Wnt and Shh signaling promote distinct dorsal-ventral patterning while also having broader effects on proliferation that serve to coordinate the growth of telencephalic subregions.