Abnormal morphogenesis in human embryos underlies congenital syndromes, such as DiGeorge syndrome and Mandibulofacial Dysostosis with Microcephaly, and results in increased morbidity and mortality. Mutations in the core components of the spliceosome result in mis-splicing, abnormal embryo development, and are responsible for a group of congenital syndromes referred to as spliceosomopathies. This research aims to identify shared cellular pathways that are regulated by these key spliceosomal genes and are perturbed in these congenital syndromes. Patients with mutation in three genes, SNRPB, SF3B4, and EFTUD2, share a constellation of defects in their midface, suggesting that these genes regulate splicing of a common set of genes responsible for midface development. Using CRISPR/Cas9 and RNAseq, we generated and characterized mutant mouse lines with conditional mutations in these three genes. Mutant embryos from these lines showed shared and gene-specific abnormalities. So far, we have identified a common pathway that is disrupted in all mutants, and we are working to explore its contribution to abnormalities found in these embryos. Our work is essential for identifying common pathways and targets which can be used to prevent or improve developmental outcomes in newborn patients with mutations in these genes.