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The Journal of Neuroscience, October 15, 2002, 22(20):8981-8991
Influence of the Embryonic Preplate on the Organization of the
Cerebral Cortex: A Targeted Ablation Model
Y.
Xie1,
E.
Skinner1,
C.
Landry2,
V.
Handley1,
V.
Schonmann1,
E.
Jacobs1,
R.
Fisher1, and
A.
Campagnoni1
1 Developmental and Molecular Neuroscience Group,
Neuropsychiatric Institute, University of California at Los Angeles,
School of Medicine, Los Angeles, California 90024-1759, and
2 Psychiatric Institute, University of Wisconsin, Madison,
Wisconsin 53719
Transgenic mice were generated to permit the targeted ablation of
cortical preplate cells at the time they are born. In these mice, the
1.3 kb golli promoter of the myelin basic protein gene was used to
drive the herpes simplex virus thymidine kinase (TK) transgene
in cortical preplate cells. Heterozygous transgenic pairs were bred,
and pregnant dams were treated with ganciclovir at embryonic days
11-12 to ablate preplate cells at the time the preplate was forming.
This paradigm exposed control (TK ) and experimental (TK+) littermates
to exactly the same conditions. Embryological ablation of preplate
cells led to an early disruption of the radial glial framework and
subplate structure in the developing cortex and dramatically altered
the cellular lamination and connectivity of the cortical plate. The
disturbed radial glial network contributed to an impaired radial
migration of neurons into the cortical plate from the ventricular zone.
The cortical plate became dyslaminated, and there was a substantial
reduction in short- and long-range cortical projections within the
cortex and to subcortical regions. Cell death within the cortical plate
and the proliferative zones was substantially increased in the ablated
animals. After birth, a cortical lesion developed, which became
exacerbated with the secondary onset of hydrocephaly in the second
postnatal week. The results underscore the critical importance of the
preplate in cortex formation, mediated through its guidance of the
formation of radial glial scaffolding, subsequent neuronal migration
into the incipient cortical plate, and the final arrangement of its vertical organization and cellular connectivity.
Key words:
preplate; cortex; development; transgenic;  -galactosidase; HSV-thymidine kinase; ablation; cell death
Copyright © 2002 Society for Neuroscience 0270-6474/02/22208981-11$05.00/0
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