The early cytoarchitectonic specialization and area-specific different
iation of the prospective entorhinal cortex were studied in the postmo
rtem human fetal brains (9.5-13.5 postovulatory weeks). At 10 weeks, u
sing the Golgi method, we saw the appearance of area-specific large ne
urons (promoter neurons) with widely bifurcating apical dendrites situ
ated at the outer margin of the cortical plate of the prospective ento
rhinal cortex. The analysis of the serial Nissl-stained sections revea
led the concomitant appearance of a one-cell-thick layer (monolayer) a
t the interface between the cortical plate and the marginal zone and m
ultilaminated spread of the deep part of the cortical plate. This is t
he earliest sign of area-specific cytoarchitectonic differentiation of
all pallial regions characterized by the presence of the typical cort
ical plate. The first subareal differentiation within the entorhinal c
ortex begins at 13 postovulatory weeks with uneven development of fibe
r-rich lamina dissecans, which separates two cellular laminae principa
les (externa and interna), and with the appearance of characteristic c
ell islands of the prospective layer II. At rostral levels, cell islan
ds begin to develop in the rostromedial entorhinal area at the subpial
depths where large promoter neurons reside. At intermediate levels, b
oth lamina dissecans and lamina principalis interna are well delineate
d. At caudal levels, lamina principalis interna is continuous with the
upper subplate zone of the adjacent neocortex. Both area-specific neu
rons (promoters) and fiber-rich (afferent) strata develop synchronousl
y during the earliest areal differentiation of the cerebral cortex. Th
e precocious lamination of the cortical plate is the crucial event in
the histogenesis of the entorhinal cortex.