Abstract
The transcription factor Pax6 is a crucial regulator of eye and central nervous system development. Both the spatiotemporal patterns and the precise levels of Pax6 expression are subject to tight control, mediated by an extensive set of cis-regulatory elements. Previous studies have shown that a YAC reporter transgene containing 420Kb of genomic DNA spanning the human PAX6 locus drives expression of a tau-tagged GFP reporter in mice in a pattern that closely resembles that of endogenous Pax6. Here we have closely compared the pattern of tau-GFP reporter expression at the cellular level in the forebrains and eyes of transgenic mice carrying either complete or truncated versions of the YAC reporter transgene with endogenous Pax6 expression and found several areas where expression of tau-GFP and Pax6 diverge. Some discrepancies are due to differences between the intracellular localization or perdurance of tau-GFP and Pax6 proteins, while others are likely to be a consequence of transcriptional differences. We show that cis-regulatory elements that lie outside the 420kb fragment of PAX6 are required for correct expression around the pallial-subpallial boundary, in the amygdala and the prethalamus. Further, we found that the YAC reporter transgene effectively labels cells that contribute to the lateral cortical stream, including cells that arise from the pallium and subpallium, and therefore represents a useful tool for studying lateral cortical stream migration.
Highlights
Pax6 encodes a highly evolutionarily conserved transcription factor with two DNA-binding domains - a paired domain and a paired-type homeodomain [1,2]
DTy54 transgenic mice carry a single copy of yeast artificial chromosome (YAC) 1123, which is a full-length version of YAC 593 modified so that it expresses tau-tagged GFP instead of PAX6 [38]
We found that tau-GFP reporter expression in the forebrain and eye of two transgenic lines (DTy54 and Y223) carrying fulllength reporter YAC transgenes derived from Y593 largely resembled that of Pax6, in agreement with previous studies [30,38]
Summary
Pax encodes a highly evolutionarily conserved transcription factor with two DNA-binding domains - a paired domain and a paired-type homeodomain [1,2]. In the forebrain, Pax is expressed in a complex and dynamic pattern, including a clear gradient of expression across the developing cerebral cortex. Graded Pax levels across the embryonic neocortex are essential for the correct specification of cortical areas and for maintaining their progenitor cell proliferation rates [15,16,17,18,19,20]. Both downregulation and overexpression of Pax in mice cause defects of the eye and brain [15,16,17,20,21]. Tight control of Pax6’s complex spatiotemporal expression pattern is essential for normal development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
