ORCID Profile
0000-0002-0489-2400
Current Organisation
The University of Edinburgh
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Publisher: Society for Neuroscience
Date: 10-2002
Publisher: Elsevier BV
Date: 12-1995
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.YDBIO.2008.12.008
Abstract: The Gli3 zinc finger transcription factor is expressed in developing forebrain, with the highest levels of expression in dorsal telencephalon. In Gli3(-/-) embryos the dorsal telencephalon is abnormally small and fails to develop dorsomedial telencephalic structures, including hippoc us and cortical hem, while the ventral telencephalon appears to expand. A hurdle to understanding the underlying mechanisms is that abnormalities of developing Gli3(-/-) telencephalic cells in Gli3(-/-) mutants result from a combination of their own cell autonomous defects and defects in the Gli3(-/-) cells that surround them. Here we used chimeras to identify some of the defects of Gli3(-/-) telencephalic cells that are likely to be autonomous by studying how Gli3(-/-) cells develop when surrounded by a majority of wild-type cells. We found that Gli3(-/-) cells are present in all components of the Gli3(-/-) Gli3(+/+) chimeric forebrain, including dorsomedial structures, in proportions that either equal or exceed proportions found elsewhere in the embryo. Gli3(-/-) cells segregate from Gli3(+/+) cells to form many abnormal structures particularly in dorsal telencephalon. Gli3(-/-) cells in some locations are misspecified: in those parts of the dorsal telencephalon near to its boundaries with the diencephalon and the ventral telencephalon, mutant cells express sets of transcription factors expressed by wild-type cells on the other side of the boundary. Elsewhere in the dorsal telencephalon, in the diencephalon and in the ventral telencephalon, mutant cells express sets of transcription factors similar to those expressed by their immediately surrounding wild-type cells. We propose that an important cell autonomous action of Gli3 is to regulate the competence of dorsal telencephalic cells, preventing cells near to its boundaries expressing regulatory factors normally restricted to adjacent tissues.
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: The Company of Biologists
Date: 02-2007
DOI: 10.1242/DEV.02764
Abstract: Levels of expression of the transcription factor Pax6 vary throughout corticogenesis in a rostro-lateralhigh to caudo-mediallow gradient across the cortical proliferative zone. Previous loss-of-function studies have indicated that Pax6 is required for normal cortical progenitor proliferation, neuronal differentiation, cortical lamination and cortical arealization, but whether and how its level of expression affects its function is unclear. We studied the developing cortex of PAX77 YAC transgenic mice carrying several copies of the human PAX6 locus with its full complement of regulatory regions. We found that PAX77 embryos express Pax6 in a normal spatial pattern, with levels up to three times higher than wild type. By crossing PAX77 mice with a new YAC transgenic line that reports Pax6 expression (DTy54), we showed that increased expression is limited by negative autoregulation. Increased expression reduces proliferation of late cortical progenitors specifically, and analysis of PAX77↔wild-type chimeras indicates that the defect is cell autonomous. We analyzed cortical arealization in PAX77 mice and found that, whereas the loss of Pax6 shifts caudal cortical areas rostrally, Pax6 overexpression at levels predicted to shift rostral areas caudally has very little effect. These findings indicate that Pax6 levels are stabilized by autoregulation, that the proliferation of cortical progenitors is sensitive to altered Pax6 levels and that cortical arealization is not.
Publisher: Springer Science and Business Media LLC
Date: 24-02-2010
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for John Mason.