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The Journal of Neuroscience, November 15, 2001, 21(22):8798-8808
disabled-1 Functions Cell Autonomously during
Radial Migration and Cortical Layering of Pyramidal Neurons
Vicki
Hammond1,
Brian
Howell2,
Leanne
Godinho1, and
Seong-Seng
Tan1
1 Howard Florey Institute, The University of Melbourne,
Parkville 3010, Victoria, Australia, and 2 National
Institute for Neurological Diseases and Stroke, National Institutes of
Health, Bethesda, Maryland 20892
Genetic mosaics offer an excellent opportunity to analyze complex
gene functions. Chimeras consisting of mutant and wild-type cells
provide not only the avenue for lineage-specific gene rescue but can
also distinguish cell-autonomous from non-cell-autonomous gene
functions. Using an independent genetic marker for wild-type cells, we
constructed Dab1+/+  Dab1 / chimeras with the aim of
discovering whether or not the function of Dab1 during neuronal
migration and cortical layering is cell autonomous.
Dab1+/+ cells were capable of radial
migration and columnar formation in a
Dab1/environment. Most
Dab1+/+ cells segregated to the
superficial part of the mutant cortex, forming a multilayered
supercortex. Neuronal birth-dating studies indicate that supercortex
neurons were correctly layered, although adjacent mutant cortex neurons
were in reversed order. Immunocytochemistry using Emx1, a marker for
pyramidal neurons, indicates that the vast majority of
Dab1+/+ neurons in the supercortex
were Emx1 immunoreactive. Confirmation of the pyramidal phenotype was
demonstrated by the absence of GABA immunoreactivity among
Dab1+/+ cells in the supercortex.
Myelin staining using 2'3'-cyclic nucleotide 3'-phosphodiesterase showed the supercortex was supported by a secondary white matter from which thick fiber tracts appear connected to the underlying mutant white matter. The presence of
Dab1+/+ cells failed to rescue inversion
of cortical layers and the abnormal infiltration of the marginal zone
by Dab1/ cells. Conversely, mutant
cells did not impose a mutant phenotype on adjacent wild-type neurons.
These results suggest that Dab1 functions cell autonomously with
respect to radial migration and cortical layering of pyramidal neurons.
Key words:
disabled-1; Reelin; development; cortex; Emx-1; radial migration
Copyright © 2001 Society for Neuroscience 0270-6474/01/21228798-11$05.00/0
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