Cleft palate: players, pathways, and pursuits

Abstract

Cleft lip and palate is a common human birth defect, and its causes are being dissected through studies of human populations and through the use of animal models. Mouse models in particular have made a substantial contribution to our understanding of the gene pathways involved in palate development and the nature of signaling molecules that act in a tissue-specific manner at critical stages of embryogenesis. Related work has provided further support for investigating the role of common environmental triggers as causal covariates.

Figure 1

Signaling molecules essential for palate development. (A) Transverse section of embryonic palate. (B) Schematic of sections of normal palate shelf (ps; blue) development at the indicated days after conception. Palate shelves emanate from maxillary prominences (E11.5), grow, and extend vertically past the tongue (E12.5). The tongue (T; pink) drops, allowing the palate shelves to elevate (E13.5), appose (E14.5), and fuse (E15.5). (C and D) Cell-specific expression of signaling molecules during palate growth (C) and fusion (D). Genes involved in palate growth may also be involved in fusion. The γ-aminobutyric acid receptor subunit β3 (Gabrb3) is also involved in palate elevation (not shown). Molecules are expressed in the epithelium (yellow) or mesenchyme (blue). Molecules shown to be essential for palate development are indicated for mouse (oval), human (underlined), and both mouse and human (rectangle). Arrows indicate known (black) or predicted (gray) gene-gene (straight) and gene-environment (wavy) interactions. Ahr, aryl-hydrocarbon receptor; Alk5, activin receptor_like kinase 5; Bmp4, bone morphogenic protein 4; Bzd’s, benzodiazepines; Msx1, msh-like 1 homeo box; Ptc, patched homolog 1; Pvrl1, poliovirus receptor_related 1; SATB2, SATB family member 2; TBX22, T-box 22; Tgfb3, transforming growth factor β3.