In situ hybridization probe sequences for mouse Alx3, Fgf8, Msx1, Shh, Six3

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.