First Author | Li Q | Year | 2014 |
Journal | Elife | Volume | 3 |
Pages | e01201 | PubMed ID | 24448406 |
Mgi Jnum | J:207976 | Mgi Id | MGI:5560390 |
Doi | 10.7554/eLife.01201 | Citation | Li Q, et al. (2014) The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation. Elife 3:e01201 |
abstractText | 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. DOI: http://dx.doi.org/10.7554/eLife.01201.001. |