The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation
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. Cultu...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2014-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/01201 |
| _version_ | 1818018566187778048 |
|---|---|
| author | Qin Li Sika Zheng Areum Han Chia-Ho Lin Peter Stoilov Xiang-Dong Fu Douglas L Black |
| author_facet | Qin Li Sika Zheng Areum Han Chia-Ho Lin Peter Stoilov Xiang-Dong Fu Douglas L Black |
| author_sort | Qin Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:41:23Z |
| format | Article |
| id | doaj.art-67db64f5578a4224962363578e38a943 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:41:23Z |
| publishDate | 2014-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-67db64f5578a4224962363578e38a9432022-12-22T02:05:29ZengeLife Sciences Publications LtdeLife2050-084X2014-01-01310.7554/eLife.01201The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturationQin Li0Sika Zheng1Areum Han2Chia-Ho Lin3Peter Stoilov4Xiang-Dong Fu5Douglas L Black6Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United StatesDepartment of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United StatesDepartment of Biochemistry, West Virginia University, School of Medicine, Morgantown, United StatesDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United StatesWe 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.https://elifesciences.org/articles/01201alternative splicingRNA binding proteinneuronal developmentgene regulation |
| spellingShingle | Qin Li Sika Zheng Areum Han Chia-Ho Lin Peter Stoilov Xiang-Dong Fu Douglas L Black The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation eLife alternative splicing RNA binding protein neuronal development gene regulation |
| title | The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation |
| title_full | The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation |
| title_fullStr | The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation |
| title_full_unstemmed | The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation |
| title_short | The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation |
| title_sort | splicing regulator ptbp2 controls a program of embryonic splicing required for neuronal maturation |
| topic | alternative splicing RNA binding protein neuronal development gene regulation |
| url | https://elifesciences.org/articles/01201 |
| work_keys_str_mv | AT qinli thesplicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT sikazheng thesplicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT areumhan thesplicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT chiaholin thesplicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT peterstoilov thesplicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT xiangdongfu thesplicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT douglaslblack thesplicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT qinli splicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT sikazheng splicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT areumhan splicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT chiaholin splicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT peterstoilov splicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT xiangdongfu splicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation AT douglaslblack splicingregulatorptbp2controlsaprogramofembryonicsplicingrequiredforneuronalmaturation |