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New genetics from Drosophila: Impacts of de novo mutations in animal development

New genetics from Drosophila: Impacts of de novo mutations in animal development

2017.11.28 13:34
2017年12月15日(金) 15:00~
片平キャンパス生命科学プロジェクト総合研究棟講義室A (104)
講演者:秋山 琢也 博士
   (Dr. Takuya Akiyama, Stowers Institute for Medical Research, USA)
 
 
Alteration of genetic information is a cause of a variety of diseases. Although pathogenesis associated with inherited mutations has been extensively studied, how de novo mutations during development and homeostasis lead to disease conditions remains elusive. To address this question, we establish an inducible allele switch system at the endogenous locus that allows replacement of wild-type coding sequence with its mutants via flippase recognition target (FRT)-mediated recombination. As a model system, we employ the Drosophila BMPR1A thickveins (tkv). In the developing wing disc, the Tkv receptor complex activates the Drosophila BMP2/4-like ligand Decapentaplegic (DPP) morphogen pathway by phosphorylating a downstream signaling transducer, Mothers against DPP (p-Mad), and directs wing pattern formation. we found that inherited heterozygous tkv mutants exhibit little effect of p-Mad expression and develop normal adult wings. In contrast, de novo tkv heterozygous mutations generating wing discs with both wild-type and heterozygous clonal cell populations disrupt proper p-Mad expression in a clone-size dependent manner, leading to wing patterning defects. We term this phenomenon “deleterious heteromosaicism.” In this seminar, I would like to discuss previously unrecognized impacts of de novo recessive heterozygous mutations in animal development and provide a new concept to understand genetic mechanisms underlying disease initiation.
 
 
 
問い合わせ先
学際科学フロンティア研究所(生命科学研究科 細胞動態制御分野)
中嶋 悠一朗 yuichiro.nakajima.d2*tohoku.ac.jp(*を@に置き換えて下さい)