Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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 beta-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 beta-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.

Type

Journal article

Journal

Development

Publication Date

11/2002

Volume

129

Pages

5041 - 5052

Keywords

Animals, Axons, Body Patterning, Cell Adhesion Molecules, Neuronal, Cerebral Cortex, Contactin 2, Eye Proteins, Gene Expression Regulation, Developmental, Homeodomain Proteins, Lac Operon, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Mice, Transgenic, Neural Pathways, PAX6 Transcription Factor, Paired Box Transcription Factors, Prosencephalon, Repressor Proteins, Thalamus