Studies on molecular mechanisms underlying abnormal neurogenesis in a mouse model of Down syndrome

Down syndrome, caused by triplication for human chromosome 21, is associated with abnormalities in brain development such as reduced production of neurons. Previous studies suggest that neuronal differentiation of progenitors in Down syndrome brains is deregulated, however, very little is known about the molecular mechanisms underlying that deregulation. In this study, we focused on intermediate progenitor cells, a type of neurogenic transient amplifying cells, and found that overexpression of a gene located in human chromosome 21 results in abnormal differentiation of intermediate progenitor cells.

ダウン症は一般に、およそ800人の新生児あたりに1人という割合で発生しており、遺伝子疾患及び染色体異常の中では最も頻度が高い。すなわち、ダウン症の治療戦略の開発は社会的要請が極めて高い。本研究では、ダウン症脳の神経前駆細胞の分化異常を引き起こすメカニズムに分子レベルで切り込み、脳発生異常に寄与する分子シグナリングを明らかにする。そのため、本研究で得られた成果はダウン症における脳機能障害の発症機序に関する理解を進め、その治療戦略に重要な示唆を与えることが期待できる。