title: Abnormal positioning of diencephalic cell types in neocortical tissue in the dorsal telencephalon of mice lacking functional Gli3.
abstract: 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 Gli3(Xt/Xt) mutant mice lacking functional Gli3. In this study, we analyzed expression of Gli3 in the wild-type telencephalon and observed a (high)dorsal-to-(low)ventral gradient of Gli3 expression and predominance of the cleaved form of the Gli3 protein dorsally. This graded expression correlates with the (severe)dorsal-to-(mild)ventral telencephalic phenotype observed in Gli3(Xt/Xt) mice. We characterized the abnormal joining of the telencephalon to the diencephalon and defined the medial limit of the dorsal telencephalon in Gli3(Xt/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 Gli3(Xt/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 Gli3(Xt/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 telencephalic-diencephalic boundary and for preventing the abnormal positioning of diencephalic cells in the dorsal telencephalon.
authors.affiliation: Genes and Development Group, Biomedical Sciences, The University of Edinburgh, Edinburgh EH8 9XD, United Kingdom. vfotaki@ed.ac.uk
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Fotaki
authors.forename: Tian
authors.initials: T
authors.lastname: Yu
authors.forename: Paulette A
authors.initials: PA
authors.lastname: Zaki
authors.forename: John O
authors.initials: JO
authors.lastname: Mason
authors.forename: David J
authors.initials: DJ
authors.lastname: Price
mesh_terms: D000818:Animals; D004027:Diencephalon / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D019579:Neocortex / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D014018:Tissue Distribution; D000074290:Zinc Finger Protein Gli3
chemical_list: C465571:Gli3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3