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

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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.