第1249回生物科学セミナー

The roles of Down syndrome genes in neuronal development and brain disorders

Prof. Bing Ye(Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, USA)

2018年11月27日(火)    14:00-15:00  理学部2号館 223号室   

Down syndrome (DS) is a common form of intellectual disability, but the molecular mechanisms that underlie neurodevelopmental disorders in DS are poorly understood. DS is caused by the trisomy of human chromosome 21 (hCh21); different aspects of DS are caused by different genes on this chromosome. In consequence, a major hurdle in developing treatments for DS is the identification of genes and molecular pathways that are the drivers of pathogenesis and can be targeted for effective therapies. We discovered that the expression level of the Down syndrome cell adhesion molecule (DSCAM) instructs the growth of presynaptic terminals in Drosophila. DSCAM levels are increased in the brains of DS patients. We thus investigated the possible role of DSCAM in the pathogenesis of DS brain disorders. We found that the presynaptic terminals of Chandelier cells (ChCs), which are a major type of inhibitory neurons in the neocortex, are overgrown in DS mouse models. Histological and physiological studies show that DSCAM plays a major role in the presynaptic overgrowth in DS mice. These findings suggest that DSCAM contributes to neurodevelopmental defects in DS, and elucidate a productive approach for identifying genes that drive the pathogenesis of DS by using Drosophila.