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

Abstract

There is accumulating evidence that the mammalian cerebral cortex is regionally specified early in neurogenesis. However, the degree and scale of the regional pattern that is intrinsic to different parts of the cortical primordium remains unclear. Here, we show that detailed patterning-the accurate positioning of several areas or fields-is intrinsic to the part of the primordium that generates the hippocampus. A caudomedial portion of the cortical 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 hippocampal 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 explants upregulate field-specific patterns of gene expression with striking temporal and spatial accuracy. Possible sources of patterning signals intrinsic to the explants were evaluated by removing the cortical hem or presumptive extrahippocampal cortex from the explants. To expose cells to different local positional cues, explant fragments were grafted into ectopic positions in a larger explant. None of these manipulations altered the development of patterned, field-specific gene expression. Finally, explants harvested at E10.5 also upregulate field-specific gene expression, although less robustly. Some hippocampal patterning information is therefore intrinsic to the caudomedial cortical primordium at the time that the first hippocampal neurons 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.