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The Journal of Neuroscience, September 1, 2002, 22(17):7627-7638
Distinct Actions of Emx1, Emx2, and
Pax6 in Regulating the Specification of Areas in the
Developing Neocortex
Kathie M.
Bishop1,
John
L. R.
Rubenstein2, and
Dennis D. M.
O'Leary1
1 Molecular Neurobiology Laboratory, The Salk Institute
for Biological Studies, La Jolla, California 92037, and
2 Nina Ireland Laboratory of Developmental Neurobiology,
Department of Psychiatry, University of California San Francisco, San
Francisco, California 94143
The mammalian neocortex is organized into subdivisions referred to
as areas that are distinguished from one another by differences in
architecture, axonal connections, and function. The transcription factors EMX1, EMX2, and PAX6 have been proposed to regulate
arealization. Emx1 and Emx2 are expressed
by progenitor cells in a low rostrolateral to high caudomedial
gradient across the embryonic neocortex, and Pax6 is
expressed in a high rostrolateral to low caudomedial gradient. Recent
evidence has suggested that EMX2 and PAX6 have a role in the genetic
regulation of arealization. Here we use a panel of seven genes
(Cad6, Cad8, Id2,
RZR , p75, EphA7,
and ephrin-A5) representative of a broad range of
proteins as complementary markers of positional identity to obtain a
more thorough assessment of the suggested roles for EMX2 and PAX6 in
arealization, and in addition to assess the proposed but untested role
for EMX1 in arealization. Orderly changes in the size and positioning
of domains of marker expression in Emx2 and
Pax6 mutants strongly imply that rostrolateral areas
(motor and somatosensory) are expanded, whereas caudomedial areas
(visual) are reduced in Emx2 mutants and that opposite
effects occur in Pax6 mutants, consistent with their opposing gradients of expression. In contrast, patterns of marker expression, as well as the distribution of area-specific
thalamocortical projections, appear normal in Emx1
mutants, indicating that they do not exhibit changes in arealization.
This lack of a defined role for EMX1 in arealization is supported by
our finding of similar shifts in patterns of marker expression in
Emx1; Emx2 double mutants as in Emx2 mutants.
Thus, our findings indicate that EMX2 and PAX6 regulate, in opposing
manners, arealization of the neocortex and impart positional identity
to cortical cells, whereas EMX1 appears not to have a role in this process.
Key words:
area identity; cadherins; corticogenesis; EphA7; ephrin-A5; Id2; p75; patterning mechanisms; positional identity; ROR; RZR; thalamocortical projections; transcription
factors
Copyright © 2002 Society for Neuroscience 0270-6474/02/22177627-12$05.00/0
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