Conditional cell ablation via diphtheria toxin reveals distinct requirements for the basal plate in the regional identity of diencephalic subpopulations.
The mammalian diencephalon is the caudal derivative of the embryonic forebrain. Early events in diencephalic regionalization include its subdivision along the dorsoventral and anteroposterior axes. The prosomeric model by Puelles and Rubenstein (1993) suggests that the alar plate of the posterior diencephalon is partitioned into three different prosomeres (designated p1-p3), which develop into the pretectum, thalamus, and prethalamus, respectively. Here, we report the developmental consequences of genetic ablation of cell populations from the diencephalic basal plate. The strategy for conditionally regulated cell ablation is based on the targeted expression of the diphtheria toxin gene (DTA) to the diencephalic basal plate via tamoxifen- induced, Cre-mediated recombination of the ROSA(DTA) allele. We show that activation of DTA leads to specific cell loss in the basal plate of the posterior diencephalon, and disrupted early regionalization of distinct alar territories. In the basal plate-deficient embryos, the p1 alar plate exhibited reduced expression of subtype-specific markers in the pretectum, whereas p2 alar plate failed to further subdivide into two discrete thalamic subpopulations. We also show that these defects lead to abnormal nuclear organization at later developmental stages. Our data have implications for increased understanding of the interactive roles between discrete diencephalic compartments.
['Lee|Bumwhee|B|', 'Lam|Duc Tri|DT|', 'Baek|Kwanghee|K|', 'Yoon|Jaeseung|J|', 'Jeong|Yongsu|Y|']
D000818:Animals D051792:Basic Helix-Loop-Helix Transcription Factors D004027:Diencephalon D004167:Diphtheria Toxin D004622:Embryo, Mammalian D050990:GATA3 Transcription Factor D018507:Gene Expression Regulation, Developmental D053823:Hedgehog Proteins D007150:Immunohistochemistry D017403:In Situ Hybridization D008822:Mice, Transgenic D038081:Organogenesis D011518:Proto-Oncogene Proteins D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1 D013997:Time Factors
basal plate regionalization diencephalon forebrain alar plate