a sox10 expression screen identifies an amino acid essential for erbb3 functionsox10表达式屏幕识别所必需的一种氨基酸erbb3函数.pdfVIP

A Sox10 Expression Screen Identifies an Amino Acid Essential for Erbb3 Function 1,2. 1. 1 1 1 Kristina Buac , Dawn E. Watkins-Chow , Stacie K. Loftus , Denise M. Larson , Arturo Incao , Gretchen 3 1 Gibney , William J. Pavan * 1 Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 2 George Washington University, Washington, D.C., United States of America, 3 Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America Abstract The neural crest (NC) is a population of embryonic stem cells that gives rise to numerous cell types, including the glia and neurons of the peripheral and enteric nervous systems and the melanocytes of the skin and hair. Mutations in genes and genetic pathways regulating NC development lead to a wide spectrum of human developmental disorders collectively called neurocristopathies. To identify molecular pathways regulating NC development and to understand how alterations in these processes lead to disease, we established an N-ethyl-N-nitrosourea (ENU) mutagenesis screen utilizing a mouse model sensitized for NC defects, Sox10LacZ/+. Out of 71 pedigrees analyzed, we identified and mapped four heritable loci, called modifier of Sox10 expression pattern 1–4 (msp1–4), which show altered NC patterning. In homozygous msp1 embryos, Sox10LacZ expression is absent in cranial ganglia, cranial nerves, and the sympathetic chain; however, the development of other Sox10-expressing cells appears unaffected by the mutation. Linkage analysis, sequencing, and complementat