Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors
Serum response factor (SRF) is an essential transcription factor that influences many cellular processes including cell proliferation, migration, and differentiation. SRF directly regulates and is required for immediate early gene (IEG) and actin cytoskeleton-related gene expression. SRF coordinates...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/75106 |
| _version_ | 1797998418844450816 |
|---|---|
| author | Colin J Dinsmore Philippe Soriano |
| author_facet | Colin J Dinsmore Philippe Soriano |
| author_sort | Colin J Dinsmore |
| collection | DOAJ |
| description | Serum response factor (SRF) is an essential transcription factor that influences many cellular processes including cell proliferation, migration, and differentiation. SRF directly regulates and is required for immediate early gene (IEG) and actin cytoskeleton-related gene expression. SRF coordinates these competing transcription programs through discrete sets of cofactors, the ternary complex factors (TCFs) and myocardin-related transcription factors (MRTFs). The relative contribution of these two programs to in vivo SRF activity and mutant phenotypes is not fully understood. To study how SRF utilizes its cofactors during development, we generated a knock-in SrfaI allele in mice harboring point mutations that disrupt SRF-MRTF-DNA complex formation but leave SRF-TCF activity unaffected. Homozygous SrfaI/aI mutants die at E10.5 with notable cardiovascular phenotypes, and neural crest conditional mutants succumb at birth to defects of the cardiac outflow tract but display none of the craniofacial phenotypes associated with complete loss of SRF in that lineage. Our studies further support an important role for MRTF mediating SRF function in cardiac neural crest and suggest new mechanisms by which SRF regulates transcription during development. |
| first_indexed | 2024-04-11T10:48:27Z |
| format | Article |
| id | doaj.art-15da44ad559a4520b46d6f8b3f3e0cb4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:48:27Z |
| publishDate | 2022-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-15da44ad559a4520b46d6f8b3f3e0cb42022-12-22T04:28:58ZengeLife Sciences Publications LtdeLife2050-084X2022-01-011110.7554/eLife.75106Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactorsColin J Dinsmore0https://orcid.org/0000-0002-6404-1202Philippe Soriano1https://orcid.org/0000-0002-0427-926XDepartment of Cell, Development and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Cell, Development and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, United StatesSerum response factor (SRF) is an essential transcription factor that influences many cellular processes including cell proliferation, migration, and differentiation. SRF directly regulates and is required for immediate early gene (IEG) and actin cytoskeleton-related gene expression. SRF coordinates these competing transcription programs through discrete sets of cofactors, the ternary complex factors (TCFs) and myocardin-related transcription factors (MRTFs). The relative contribution of these two programs to in vivo SRF activity and mutant phenotypes is not fully understood. To study how SRF utilizes its cofactors during development, we generated a knock-in SrfaI allele in mice harboring point mutations that disrupt SRF-MRTF-DNA complex formation but leave SRF-TCF activity unaffected. Homozygous SrfaI/aI mutants die at E10.5 with notable cardiovascular phenotypes, and neural crest conditional mutants succumb at birth to defects of the cardiac outflow tract but display none of the craniofacial phenotypes associated with complete loss of SRF in that lineage. Our studies further support an important role for MRTF mediating SRF function in cardiac neural crest and suggest new mechanisms by which SRF regulates transcription during development.https://elifesciences.org/articles/75106SRFMRTFTCFcraniofacial developmentneural cresttranscription |
| spellingShingle | Colin J Dinsmore Philippe Soriano Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors eLife SRF MRTF TCF craniofacial development neural crest transcription |
| title | Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors |
| title_full | Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors |
| title_fullStr | Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors |
| title_full_unstemmed | Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors |
| title_short | Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors |
| title_sort | differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors |
| topic | SRF MRTF TCF craniofacial development neural crest transcription |
| url | https://elifesciences.org/articles/75106 |
| work_keys_str_mv | AT colinjdinsmore differentialregulationofcranialandcardiacneuralcrestbyserumresponsefactoranditscofactors AT philippesoriano differentialregulationofcranialandcardiacneuralcrestbyserumresponsefactoranditscofactors |