TTC21B and spina bifida: Experiments directly testing Gpr63 function with novel mouse alleles generated with CRISPR-Cas9 genome editing support our hypothesis that reduced Gpr63 function further compromises embryos lacking functional Ttc21b. We further demonstrated that Gpr63;Ttc21b double mutants had earlier lethality than either single mutant as well as novel spina bifida phenotypes.