Orofacial clefting: recent insights into a complex trait

Abstract

Orofacial clefts are common birth defects of multifactorial etiology. Several novel approaches have recently been applied to investigate the causes of clefts. These include examining Mendelian forms of clefting to identify genes that might also be implicated in isolated clefting, analyzing chromosomal rearrangements in which clefting is part of the resultant phenotype, studying animal models in which clefts arise either spontaneously or as a result of mutagenesis experiments, exploring how expression patterns correlate with gene function and examining the effects of gene-environment interactions. Together, these complementary strategies are providing researchers with new clues as to what mechanisms underlie orofacial clefting.

Figure 1

Irf6 expression in the E14.5 prefusion mouse palate. The figure depicts an in situ frontal section through the posterior palate. Nuclei were stained with DAPI for background staining and the silver grains were pseudo-colored red in the merged image. (Photograph kindly provided by Alexandra Knight and Professor Michael J Dixon).

Figure 2

Satb2 expression during development of the murine secondary palate. Whole-mount in situ hybridization analysis of Satb2 expression in mouse embryos at (a) E13.5 and (b) E14.5. (a) At E13.5, the strongest expression of Satb2 is detected in the mesenchyme underlying the presumptive medial edge epithelia (arrows). (b) By the time of palatal shelf fusion at E14.5, the expression is dramatically down-regulated. Abbreviations: PS, palatal shelf. (Photographs kindly provided by Professor Michael J Dixon).