School of Medicine
We show that the splicing regulator PTBP2 controls a genetic program essential for neuronal maturation. Depletion of PTBP2 in developing mouse cortex leads to degeneration of these tissues over the first three postnatal weeks, a time when the normal cortex expands and develops mature circuits. Cultured Ptbp2−/−neurons exhibit the same initial viability as wild type, with proper neurite outgrowth and marker expression. However, these mutant cells subsequently fail to mature and die after a week in culture. Transcriptome-wide analyses identify many exons that share a pattern of mis-regulation in the mutant brains, where isoforms normally found in adults are precociously expressed in the developing embryo. These transcripts encode proteins affecting neurite growth, pre- and post-synaptic assembly, and synaptic transmission. Our results define a new genetic regulatory program, where PTBP2 acts to temporarily repress expression of adult protein isoforms until the final maturation of the neuron.
Digital Commons Citation
Li, Qin; Zhaeng, Sika; Han, Areum; Lin, Chia-Ho; Stoilov, Peter; Fu, Xiang-Dong; and Black, Douglas L., "The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation" (2014). Faculty & Staff Scholarship. 2599.
Abstract. (n.d.). eLife Sciences Publications, Ltd. https://doi.org/10.7554/elife.01201.001