Identification of genomic regions regulating Pax6 expression in embryonic forebrain using YAC reporter transgenic mouse lines.
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 420 Kb 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 420 kb 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.
Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Da
D
Mi
Yu-Ting
YT
Huang
Dirk A
DA
Kleinjan
John O
JO
Mason
David J
DJ
Price
D000818:Animals; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016548:Prosencephalon / Q000196:embryology* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins