We are interested in the early mechanisms that initiate regional patterning
in the dorsal telencephalon, which gives rise to cerebral cortex. Members
of the LIM-homeodomain (LIM-HD) family of transcription factors are implica
ted in patterning and cell fate specification in several systems including
the mammalian forebrain. Mice in which Lhx2 is disrupted were reported to h
ave reduced telencephalic development, and the hippocampal primordium appea
red to be missing, by morphological observation. We hypothesized that this
may be due to a defect in the cortical hem, a Wnt- and Bmp-rich putative si
gnaling center in the medial telencephalon, a source of regulatory signals
for hippocampal development. We asked if the expression of any known hem-sp
ecific signaling molecule is deficient in Lhx2 -/- mice. Our results reveal
, unexpectedly, that at embryonic day (E)12.5, what appears to be some spar
ed 'lateral' cortex is instead an expanded cortical hem. Normally restricte
d to the extreme medial edge of the telencephalon, the hem covers almost th
e entire dorsal telencephalon in the Lhx2-/- mice. This indicates a role fo
r Lhx2 in the regulation of the extent of the cortical hem. In spite of an
expanded, mislocated hem in the Lhx2 -/- telencephalon, a potential source
of ectopic dorsalizing cues, no hippocampal differentiation is detected in
tissue adjacent to the mutant hem, nor does the overall dorsoventral patter
ning appear perturbed. We propose that Lhx2 is involved at a crucial early
step in patterning the telencephalon, where the neuroepithelium is first di
vided into presumptive cortical tissue, and the cortical hem. The defect in
the Lhx2 -/- telencephalon appears to be at this step. (C) 2001 Elsevier S
cience Ireland Ltd. All rights reserved.