PTB/nPTB switch: a post-transcriptional mechanism for programming neuronal differentiation: Figure 1.

Neuronal differentiation involves extensive reprogramming of gene expression. Many neuronal-specific genes are actively repressed in nonneuronal cells, while many others are induced in response to cell differentiation cues. Together these constitute the transcriptome in neurons to instruct specific neuronal functions (Rosenfeld et al. 2006). The transcriptome in neurons is further diversified by alternative splicing, arising from the expression of a number of neuronal-specific RNA-binding splicing regulators (Black and Grabowski 2003). In this issue of Genes & Development, Boutz et al. (2007b) report a novel switch in the expression of a pair of related splicing regulators that occurs during neuronal differentiation. These proteins, known as polypyrimidine tractbinding proteins (PTB) and neural PTB (nPTB), are structurally and functionally similar, but PTB is widely expressed in nonneuronal cells, and nPTB is restricted to neurons. Remarkably, ∼25% of neuronally induced alternative splicing events detected by mRNA isoform-sensitive splicing arrays are estimated to result from the down-regulation of PTB, and the up-regulation of its neuronal-specific cousin nPTB.