The entorhinal cortex gives rise to a massive projection to
the hippocampus and fascia dentata. In the rat, this projection
forms early in development with first entorhinal axons reaching
the hippocampus around embryonic day (E) 17. From the very beginning,
the entorhinal axons recognize their appropriate termination
zones in the hippocampus proper and fascia dentata, i.e., stratum
lacunosum-moleculare and the outer molecular layer of the dentate.
This is remarkable, because at the time of entorhinal fiber
ingrowth, the definitive target cells of entorhinal axons, pyramidal
cells and granule cells, are not yet fully developed, and the
majority of their distal dendritic tips have not yet reached
these layers. This raises the question as to the cellular and
molecular signals guiding the entorhinal axons to and keeping
them in their target layers. Here we hypothesize that early
generated Cajal-Retzius (CR) cells located in stratum lacunosum-moleculare
and the outer molecular layer of the dentate, and in particular
their axons projecting to the entorhinal cortex, provide a template
that is used by the entorhinal axons to find their target layers
in the hippocampus.
