Differential regulation of cranial and cardiac neural crest by Serum Response Factor

The goal of this experiment was to identify genes regulated by Serum Response Factor (SRF) in the neural crest in the craniofacial region, including whether there were different targets in different craniofacial prominences. 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. 16 total samples were anlyzed from eight E11.5 mouse embryos. These consist of four control and four conditional Srf mutant mice. Each mouse had two samples, one from the mandible and one from the frontonasal prominence (i.e. lateral and medial nasal processes)