The regulatory role for the RNA binding polypyrimidine tract-binding (PTB) protein during neural development.

PTB （polyypyrimidine tract binding）蛋白是一种众所周知的多功能RNA结合蛋白，它通过与富含多嘧啶的靶前RNA和mRNA序列相互作用，调节mRNA的稳定性、内部核糖体进入位点（IRES）依赖翻译、mRNA的定位和选择性剪接（AS）。我们培育了PTB敲除小鼠和空白ESCs，发现PTB对小鼠早期发育至关重要，对小鼠ESCs的增殖和分化也很重要。它在包括神经干细胞在内的多种组织细胞中均有表达，并在神经分化过程中逐渐下调表达。一些体外研究表明，PTB的敲除导致广泛的AS事件的变化，类似于神经分化过程中观察到的变化。为了探索PTB在发育小鼠大脑中的作用，我们产生了条件PTB敲除小鼠（nesting - cre; PTB flox/neo），并通过组织学分析研究了其表型。我们的研究结果表明，PTB在发育中的小鼠大脑中的耗竭最终发展为脑积水，并清楚地表明PTB对维持背端脑粘附连接很重要，并可能在维持NSCs的过程中调节系统细胞生态位完整性。

PTB (Polypyrimidine tract binding) protein is a well-known multifunctional RNA binding protein, which can regulate mRNA stability, internal ribosome entry site (IRES) dependent translation, mRNA localization and alternative splicing (AS) by interacting with polypyrimidine rich sequences of target pre-RNAs and mRNAs. We have generated PTB knockout mice and null ESCs and found that PTB is essential for early mouse development and important for proliferation and differentiation of mouse ESCs. Its expression is observed various tissues and cells including neural stem cells (NSCs) and the expression was gradually down regulated during neural differentiation. Some in vitro studies demonstrated that knockdown of PTB leads to change of wide spread AS events similar to the change observed during neural differentiation. To explore the role of PTB in the developmental mouse brain, we generated conditional Ptb knockout mice (Nestin-Cre;Ptb flox/neo) and studied its phenotypes using histologlanalysis. Our findings show that the depletion of PTB in the developing mouse brain is eventually developed hydrocephalus and clearly reveal that PTB is important for the maintenance of adherens junctions in the dorsal telencephalon and might function in the regulation ofstem cell niche integrity upon the maintenace of NSCs.