EARLY SPECIFICATION AND AUTONOMOUS DEVELOPMENT OF CORTICAL FIELDS IN THE MOUSE HIPPOCAMPUS

Studies of the specification of distinct areas in the developing cereb ral cortex have until now focused mainly on neocortex, We demonstrate that the hippocampus, an archicortical structure, offers an elegant, a lternative system in which to explore cortical area specification. Ind ividual hippocampal areas, called CA fields, display striking molecula r differences in maturity. We use these distinct patterns of gene expr ession as markers of CA field identity, and show that the two major hi ppocampal fields, CA1 and CA3, are specified early in hippocampal deve lopment, during the period of neurogenesis. Two field-specific markers display consistent patterns of expression from the embryo to the adul t. Presumptive CA1 and CA3 fields (Pca1, Pca3) can therefore be identi fied between embryonic days 14.5 and 15.5 in the mouse, a week before the fields are morphologically distinct. No other individual cortical areas have been detected by gene expression as early in development. I ndeed, other features that distinguish between the CA fields appear af ter birth, indicating that mature CA field identity is acquired over a t least 3 weeks. To determine if Peal and Pca3 are already specified t o acquire mature CA field identities, the embryonic fields were isolat ed from further potential specification cues by maintaining them in sl ice culture, CA field development proceeds in slices of the entire emb ryonic hippocampus. More strikingly, slices restricted to Peal or Pca3 alone also develop appropriate mature features of CA1 or CA3, Pca1 an d Pca3 are therefore able to develop complex characteristics of mature CA field identity autonomously, that is, without contact or innervati on from other fields or other parts of the brain. Because Pca1 and Pca -7 can be identified before major afferents grow into the hippocampus, innervation may also be unnecessary for the initial division of the h ippocampus into separate fields. Providing a clue to the source of the true specifying signals, the earliest field markers appear first at t he poles of the hippocampus, then progress inwards. General hippocampa l development does not follow this pronounced pattern, We suggest that the sources of signals that specify hippocampal field identity lie cl ose to the hippocampal poles, and that the signals operate first on ce lls at the poles, then move inwards.