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1 Department of Human Anatomy and Genetics, University of Oxford, South Parks
Road, Oxford OX1 3QX, UK
2 Max-Planck Institute of Biophysical Chemistry, Department of Molecular Cell
Biology, 37077 Gottingen, Germany
Author for correspondence (e-mail:
zoltan.molnar{at}anat.ox.ac.uk)
Accepted 25 July 2002
The transcription factor PAX6 has been implicated in forebrain patterning, cerebral cortical arealization and in development of thalamocortical connections. Using a Pax6/lacZ knockout mouse, in which the endogenous Pax6 expression is reflected by ß-galactosidase activity, we have studied the consequences of the loss of Pax6 function on thalamocortical (TCA) and corticofugal axon (CFA) pathfinding during the period of embryonic day (E) 14.5 to E18.5. Carbocyanine dye tracing in Pax6 heterozygotes (Pax6+/-) and Pax6 wild-type (Pax6+/+) brains revealed that CFAs and TCAs temporarily arrested their growth at E14.5 at the border of the ß-galactosidase-positive region at the pallial/subpallial boundary (PSPB), before they continued towards their targets. However, in Pax6 homozygous (Pax6-/-) embryos, CFAs and TCAs were unable to encounter each other at the PSPB and reach their final targets. Instead of crossing the PSPB, they had the tendency to descend into the ventral pallium in large aberrant fascicles. In addition, cells with a presumptive guide-post function, which are normally situated in the ventral thalamus, internal capsule and hypothalamus, were more dispersed in the hypothalamus and ventral pallium. These pathfinding defects were confirmed by immunohistochemistry for L1 and TAG1, markers of the early axonal connections. The aberrant development of axonal connections in absence of Pax6 function appear to be related to ultrastructural defects of cells along the PSPB, as well as to a failure of axonal guidance molecule expression, including Sema3c and Sema5a.
Key words: Axon guidance, Patterning, Telencephalon, Semaphorins, Mouse, Pallial/subpallial boundary, Thalamocortical projections, Corticofugal axons, Mouse
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