Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors

Abstract
Data availability
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Abstract

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 Srf^aI allele in mice harboring point mutations that disrupt SRF-MRTF-DNA complex formation but leave SRF-TCF activity unaffected. Homozygous Srf^aI/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.

Data availability

The NGS data is available on GEO. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186770

The following data sets were generated

1. Dinsmore CJ
2. Soriano P
(2021) Differential regulation of cranial and cardiac neural crest by Serum Response Factor
NCBI Gene Expression Omnibus, GSE186770.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186770

Article and author information

Author details

Colin J Dinsmore

Department of Cell, Development and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, United States

Competing interests
The authors declare that no competing interests exist.
Philippe Soriano

Department of Cell, Development and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, United States

For correspondence
philippe.soriano@mssm.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0427-926X

Funding

National Institute of Dental and Craniofacial Research (R01 DE022363)

Philippe Soriano

National Institute of Dental and Craniofacial Research (F32 DE026678)

Colin J Dinsmore

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experimentation was conducted according to protocols approved by the Institutional Animal Care and Use Committee of the Icahn School of Medicine at Mount Sinai under protocol LA11-00243. Mice were kept in a dedicated animal vivarium with veterinarian support. They were housed on a 13hr-11hr light-dark cycle and had access to food and water ad libitum.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.