The genes Emx1 and Emx2 are mouse cognates of a Drosophila head gap ge
ne, empty spiracles, and their expression patterns have suggested thei
r involvement in regional patterning of the forebrain. To define their
functions we introduced mutations into these loci. The newborn Emx2 m
utants displayed defects in archipallium structures that are believed
to play essential roles in learning, memory and behavior: the dentate
gyrus was missing, and the hippocampus and medial limbic cortex were g
reatly reduced in size. In contrast, defects were subtle in adult Emx1
mutant brain. In the early developing Emx2 mutant forebrain, the evag
ination of cerebral hemispheres was reduced and the roof between the h
emispheres was expanded, suggesting the lateral shift of its boundary.
Defects were not apparent, however, in the region where Emx1 expressi
on overlaps that of Emx2, nor was any defect found in the early embryo
nic forebrain caused by mutation of the Emx1 gene, of which expression
principally occurs within the Emx2-positive region. Emx2 most likely
delineates the palliochoroidal boundary in the absence of Emx1 express
ion during early dorsal forebrain patterning. In the more lateral regi
on of telencephalon, Emx2-deficiency may be compensated for by Emx1 an
d vice versa. Phenotypes of newborn brains also suggest that these gen
es function in neurogenesis corresponding to their later expressions.