Title: "Analysis of neural crest deficit in Down syndrome mice"
Speaker: Dr. Randall Roper, Department of Biology, IUPUI, Indianapolis, IN.
Place: Electrical Engineering (EE) 270; April 3, 2007, Tuesday, 4:30pm


Trisomy 21 is one of the most prevalent serious birth defects of genetic origin and results in Down syndrome (DS). The mechanisms by which genes in three copies on human chromosome 21 (Hsa21) cause developmental abnormalities leading to DS phenotypes are not well understood. Craniofacial dysmorphology is characteristic of all individuals with DS. Ts65Dn mice are trisomic for orthologs of about half of the genes on Hsa21 and exhibit DS-like craniofacial abnormalities including brachycephaly, shortened midface, and hypomorphic mandible. Because many tissues affected in DS, including craniofacial skeleton, have a neural crest (NC) component, it has been hypothesized that trisomy 21 causes a defect in NC. Using unbiased stereology to quantify NC in the mandibular precursor, I provide the first direct experimental evidence that trisomy affects NC. Ts65Dn embryos display a paucity of NC and a reduction in the size of the mandibular precursor at midgestation as compared to euploid littermates. Further quantitative analysis suggests deficits in trisomic NC generation, migration, and proliferation. We are using cellular, genetic, and bioinformatic approaches to characterize the trisomic NC defect. Identifying how trisomy 21 disrupts NC and leads to mandibular abnormalities suggests common molecular mechanisms relevant to other neural crest-related DS phenotypes. Knowledge of how and when trisomic genes affect neural crest provides information for amelioration or prevention of these DS phenotypes.

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