Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturation
The generation of diverse neuronal subtypes involves specification of neural progenitors and, subsequently, postmitotic neuronal differentiation, a relatively poorly understood process. Here, we describe a mechanism whereby the neurotrophic factor NGF and the transcription factor Runx1 coordinate po...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/10874 |
| _version_ | 1811227917879869440 |
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| author | Siyi Huang Kevin J O'Donovan Eric E Turner Jian Zhong David D Ginty |
| author_facet | Siyi Huang Kevin J O'Donovan Eric E Turner Jian Zhong David D Ginty |
| author_sort | Siyi Huang |
| collection | DOAJ |
| description | The generation of diverse neuronal subtypes involves specification of neural progenitors and, subsequently, postmitotic neuronal differentiation, a relatively poorly understood process. Here, we describe a mechanism whereby the neurotrophic factor NGF and the transcription factor Runx1 coordinate postmitotic differentiation of nonpeptidergic nociceptors, a major nociceptor subtype. We show that the integrity of a Runx1/CBFβ holocomplex is crucial for NGF-dependent nonpeptidergic nociceptor maturation. NGF signals through the ERK/MAPK pathway to promote expression of Cbfb but not Runx1 prior to maturation of nonpeptidergic nociceptors. In contrast, transcriptional initiation of Runx1 in nonpeptidergic nociceptor precursors is dependent on the homeodomain transcription factor Islet1, which is largely dispensable for Cbfb expression. Thus, an NGF/TrkA-MAPK-CBFβ pathway converges with Islet1-Runx1 signaling to promote Runx1/CBFβ holocomplex formation and nonpeptidergic nociceptor maturation. Convergence of extrinsic and intrinsic signals to control heterodimeric transcription factor complex formation provides a robust mechanism for postmitotic neuronal subtype specification. |
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| format | Article |
| id | doaj.art-486e6ec530d44553b2d89cd7b36acbc1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:48:35Z |
| publishDate | 2015-09-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-486e6ec530d44553b2d89cd7b36acbc12022-12-22T03:37:52ZengeLife Sciences Publications LtdeLife2050-084X2015-09-01410.7554/eLife.10874Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturationSiyi Huang0Kevin J O'Donovan1Eric E Turner2Jian Zhong3David D Ginty4Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States; Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, United StatesBurke Medical Research Institute, Weill Medical College of Cornell University, White Plains, United StatesSeattle Children's Hospital, Seattle Children's Research Institute, Seattle, United StatesBurke Medical Research Institute, Weill Medical College of Cornell University, White Plains, United StatesDepartment of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States; Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, United StatesThe generation of diverse neuronal subtypes involves specification of neural progenitors and, subsequently, postmitotic neuronal differentiation, a relatively poorly understood process. Here, we describe a mechanism whereby the neurotrophic factor NGF and the transcription factor Runx1 coordinate postmitotic differentiation of nonpeptidergic nociceptors, a major nociceptor subtype. We show that the integrity of a Runx1/CBFβ holocomplex is crucial for NGF-dependent nonpeptidergic nociceptor maturation. NGF signals through the ERK/MAPK pathway to promote expression of Cbfb but not Runx1 prior to maturation of nonpeptidergic nociceptors. In contrast, transcriptional initiation of Runx1 in nonpeptidergic nociceptor precursors is dependent on the homeodomain transcription factor Islet1, which is largely dispensable for Cbfb expression. Thus, an NGF/TrkA-MAPK-CBFβ pathway converges with Islet1-Runx1 signaling to promote Runx1/CBFβ holocomplex formation and nonpeptidergic nociceptor maturation. Convergence of extrinsic and intrinsic signals to control heterodimeric transcription factor complex formation provides a robust mechanism for postmitotic neuronal subtype specification.https://elifesciences.org/articles/10874NGFRunx1/CBFBnociceptor differentiationconvergence of extrinsic and intrinsic factors |
| spellingShingle | Siyi Huang Kevin J O'Donovan Eric E Turner Jian Zhong David D Ginty Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturation eLife NGF Runx1/CBFB nociceptor differentiation convergence of extrinsic and intrinsic factors |
| title | Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturation |
| title_full | Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturation |
| title_fullStr | Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturation |
| title_full_unstemmed | Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturation |
| title_short | Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturation |
| title_sort | extrinsic and intrinsic signals converge on the runx1 cbfβ transcription factor for nonpeptidergic nociceptor maturation |
| topic | NGF Runx1/CBFB nociceptor differentiation convergence of extrinsic and intrinsic factors |
| url | https://elifesciences.org/articles/10874 |
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