Detailed field pattern is intrinsic to the embryonic mouse hippocampus early in neurogenesis

There is accumulating evidence that the mammalian cerebral cortex is region ally specified early in neurogenesis. However, the degree and scale of the regional pattern that is intrinsic to different parts of the cortical primo rdium remains unclear. Here, we show that detailed patterning-the accurate positioning of several areas or fields-is intrinsic to the part of the prim ordium that generates the hippocampus. A caudomedial portion of the cortica l primordium, the site from which the hippocampus arises, was isolated from potential extrinsic patterning cues by maintaining it in explant culture. Explants were prepared at embryonic day (E) 12.5, which is early in hippoca mpal neurogenesis in the mouse and 3 d before individual fields are seen by differential gene expression. Allowed to develop for 3 d in vitro, E12.5 e xplants upregulate field-specific patterns of gene expression with striking temporal and spatial accuracy. Possible sources of patterning signals intr insic to the explants were evaluated by removing the cortical hem or presum ptive extrahippocampal cortex from the explants. To expose cells to differe nt local positional cues, explant fragments were grafted into ectopic posit ions in a larger explant. None of these manipulations altered the developme nt of patterned, field-specific gene expression. Finally, explants harveste d at E10.5 also upregulate field-specific gene expression, although less ro bustly. Some hippocampal patterning information is therefore intrinsic to t he caudomedial cortical primordium at the time that the first hippocampal n eurons are born at E10.5. By E12.5, hippocampal field patterning appears to be well established and resistant to the manipulation of several potential intrinsic cues.