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

PTB（Polypyrimidine tract binding）蛋白是一种多功能的RNA结合蛋白，通过与靶前体RNA和mRNA中富含多聚嘧啶的序列相互作用，调节mRNA的稳定性、依赖于内部核糖体进入位点（IRES）的翻译、mRNA定位和选择性剪接（AS）。我们已经产生了PTB基因敲除小鼠和空胚胎干细胞，并发现PTB是小鼠早期发育所必需的，对小鼠胚胎干细胞的增殖和分化很重要。它在包括神经干细胞在内的多种组织和细胞中均有表达，且在神经分化过程中表达逐渐下调。一些体外研究表明，PTB的敲低导致广泛的AS事件的变化类似于在神经分化期间观察到的变化。为了探索PTB在小鼠脑发育中的作用，我们产生了条件性Ptb基因敲除小鼠（Nestin-Cre;Ptb flox/neo），并使用组织学分析研究了其表型。我们的研究结果表明，PTB在发育中的小鼠脑中的耗尽最终发展为脑积水，并且清楚地揭示了PTB对于端脑背侧的粘附连接的维持是重要的，并且可能在NSCs维持后的干细胞生态位完整性的调节中起作用。

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.