Figure 8. Changes in the expression of the two PTB proteins define three splicing regulatory states during neuronal differentiation.
Neuronal progenitor cells primarily express PTBP1. When these cells are induced to differentiate, PTBP1 is repressed and PTBP2 is induced. This switch in RNA binding proteins causes changes in the splicing of exons that are more sensitive to PTBP1 such as exon 8 of the Cacna1c calcium channel transcript. Other exons that are sensitive to both proteins maintain their repression during the early stages of neuron differentiation, when PTBP2 is high. When these cells finally mature and form synapses, PTBP2 is downregulated. This leads to changes in a splicing regulatory program that includes exons in Cam Kinase 2 and Dynamin 1. These exons are found in mRNA isoforms associated with adult brain and are precociously expressed in PTBP2 knockout brains, leading to cell death prior to final maturation.