A local Wnt-3a signal is required for development of the mammalian hippocampus.

The mechanisms that regulate patterning and growth of the developing cerebral cortex remain unclear. Suggesting a role for Wnt signaling in these processes, multiple Wnt genes are expressed in selective patterns in the embryonic cortex. We have examined the role of Wnt-3a signaling at the caudomedial margin of the developing cerebral cortex, the site of hippocampal development. We show that Wnt-3a acts locally to regulate the expansion of the caudomedial cortex, from which the hippocampus develops. In mice lacking Wnt-3a, caudomedial cortical progenitor cells appear to be specified normally, but then underproliferate. By mid-gestation, the hippocampus is missing or represented by tiny populations of residual hippocampal cells. Thus, Wnt-3a signaling is crucial for the normal growth of the hippocampus. We suggest that the coordination of growth with patterning may be a general role for Wnts during vertebrate development.