Figure 4. Cytoskeletal SPECC1L and ciliary THM1 genetically interact and affect palatogenesis.

A. Specc1l^ΔEx4/+ single heterozygotes did not exhibit cleft palate (CP), while 10% of Specc1l^ΔEx4/ΔEx4 homozygous mutants showed CP. Double heterozygous Specc1l^ΔEx4/+; Thm1^aln/+ embryos displayed 21.6% CP penetrance, and Specc1l^ΔEx4/ΔEx4; Thm1^aln/+ compound mutants exhibited 58.3% CP, consistent with a genetic interaction (** <0.002, z-statistic, Error bar represents Mean ± standard deviation (SD)). B-E. E17.5 palate (top) and forelimb digit (bottom) images from WT (B), Thm1^aln/+ (C), Specc1l^ΔEx4/ΔEx4 (D), Specc1l^ΔEx4/ΔEx4; Thm1^{aln/+ +} (E), showing worsened digit fusion in compound mutants (D vs. E). F. Specc1l^ΔCCD2+ single heterozygotes showed 18% CP, which increased to 35% CP in Specc1l^ΔCCD2/+;Thm1^aln/+ double heterozygous embryos, consistent with a genetic interaction (* <0.017, z-statistic, Mean ± standard deviation (SD)). G-J. WT (G) and Specc1l^{ΔCCD2/ΔCCD2} (H) embryos did not show any gross abnormalities at E18.5. In contrast, the Specc1l^{ΔCCD2/ΔCCD2}; Thm1^aln/+ compound mutant (I) showed a worsened phenotype with edema and craniofacial anomalies similar to those observed in Thm1^aln/aln mutant embryo (J).