The Journal of Neuroscience, October 1, 2002, 22(19):8523-8531
Disruption of Early Events in Thalamocortical Tract Formation in
Mice Lacking the Transcription Factors Pax6 or Foxg1
Thomas
Pratt1,
Jane C.
Quinn1,
T. Ian
Simpson1,
John D.
West2,
John O.
Mason1, and
David J.
Price1
1 Biomedical Sciences and 2 Department of
Reproductive and Developmental Sciences, Genes and Development Group,
University of Edinburgh, Edinburgh EH8 9XD, United Kingdom
Early events in the formation of the thalamocortical tract remain
poorly understood. Recent work has suggested that thalamocortical axons
follow a path pioneered by transient thalamic afferents originating
from the medial part of the ventral telencephalon. We studied the
development of these transient afferents and the thalamocortical tract
in mutant mice lacking transcription factors normally expressed in the
dorsal thalamus or ventral telencephalon. Pax6 is expressed in
the dorsal thalamus, but not in the medial part of the ventral
telencephalon, and the thalamocortical tract fails to form in
Pax6
/ embryos. We
found that transient thalamic afferents from the ventral telencephalon
do not form in Pax6/
embryos; this may contribute to the failure of their thalamocortical development. The distribution of
Pax6/ cells in
Pax6/
Pax6+/+ chimeras supports conclusions
drawn from forebrain marker gene expression that Pax6 is not required
for the normal development of the medial part of the ventral
telencephalon but is required in the dorsal thalamus. Failure of the
transient afferent pathway to develop is therefore likely a cell
nonautonomous defect reflecting primary defects in the thalamus. We
then examined the formation of thalamic afferents and efferents in
Foxg1/ embryos, which
lack recognizable ventral telencephalic structures. In these embryos
thalamic efferents navigate correctly through the thalamus but fail to
turn laterally into the telencephalon, whereas other axons are able to
cross the diencephalic/telencephalic boundary. Our results support a
role for the ventral telencephalon in guiding the early development of
the thalamocortical tract and identify a new role for the transcription
factor Pax6 in regulating the ability of the thalamus to attract
ventral telencephalic afferents.
Key words:
thalamocortical tract; diencephalon; ventral
telencephalon; Pax6; Foxg1; transcription factor; axon guidance; chimera; optic tract; mouse; transient thalamic afferents; tract
tracing
Copyright © 2002 Society for Neuroscience 0270-6474/02/22198523-09$05.00/0
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