The Journal of Neuroscience, September 6, 2006, 26(36):9282-9292; doi:10.1523/JNEUROSCI.2673-06.2006
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Development/Plasticity/Repair
Abnormal Positioning of Diencephalic Cell Types in Neocortical Tissue in the Dorsal Telencephalon of Mice Lacking Functional Gli3
Vassiliki Fotaki,
Tian Yu, *
Paulette A. Zaki, *
John O. Mason, and
David J. Price
Genes and Development Group, Biomedical Sciences, The University of Edinburgh, Edinburgh EH8 9XD, United Kingdom
Correspondence should be addressed to Dr. Vassiliki Fotaki, Genes and Development Group, Biomedical Sciences, George Square, The University of Edinburgh, Edinburgh EH8 9XD, UK. Email: vfotaki{at}ed.ac.uk
The transcription factor Gli3 (glioma-associated oncogene homolog) is essential for normal development of the mammalian forebrain. One extreme requirement for Gli3 is at the dorsomedial telencephalon, which does not form in Gli3Xt/Xt mutant mice lacking functional Gli3. In this study, we analyzed expression of Gli3 in the wild-type telencephalon and observed a highdorsal-to-lowventral gradient of Gli3 expression and predominance of the cleaved form of the Gli3 protein dorsally. This graded expression correlates with the severedorsal-to-mildventral telencephalic phenotype observed in Gli3Xt/Xt mice. We characterized the abnormal joining of the telencephalon to the diencephalon and defined the medial limit of the dorsal telencephalon in Gli3Xt/Xt mice early in corticogenesis. Based on this analysis, we concluded that some of the abnormal expression of ventral telencephalic markers previously described as being in the dorsal telencephalon is, in fact, expression in adjacent diencephalic tissue, which expresses many of the same genes that mark the ventral telencephalon. We observed occasional cells with diencephalic character in the Foxg1 (forkhead box)-expressing Gli3Xt/Xt telencephalon at embryonic day 10.5, a day after the anatomical subdivision of the forebrain vesicle. Large clusters of such cells appear in the Gli3Xt/Xt neocortical region at later ages, when the neocortex becomes highly disorganized, forming rosettes comprising mainly neural progenitors. We propose that Gli3 is indispensable for formation of an intact telencephalicdiencephalic boundary and for preventing the abnormal positioning of diencephalic cells in the dorsal telencephalon.
Key words: Gli3; mutant; development; telencephalon; diencephalon; eminentia thalami
Received Jan. 6, 2006;
revised July 26, 2006;
accepted July 28, 2006.
Correspondence should be addressed to Dr. Vassiliki Fotaki, Genes and Development Group, Biomedical Sciences, George Square, The University of Edinburgh, Edinburgh EH8 9XD, UK. Email: vfotaki{at}ed.ac.uk