Developmental expression analysis of the mouse and chick orthologues of IRF6: The gene mutated in Van der Woude syndrome

Abstract

Development of the lip and palate involves a complex series of events that are frequently disturbed resulting in the congenital anomalies cleft lip and cleft palate. Van der Woude syndrome (VWS) is an autosomal dominant disorder that is characterised by cleft lip, cleft palate, lower lip pits, and hypodontia. VWS arises as the result of mutations in the gene encoding interferon regulatory factor 6 (IRF6). To provide insights into the role of IRF6 during embryogenesis, we have analysed the expression of this molecule during mouse and chick facial development. Irf6 was expressed in the ectoderm covering the facial processes during their fusion to form the upper lip and primary palate in both mouse and chick. However, while Irf6 was expressed in the medial edge epithelia of the developing secondary palate of the mouse, which fuses as in man, Irf6 was not expressed in the medial edge epithelia of the naturally cleft chick secondary palate. Similarly, Irf6 was found to be down-regulated in the medial edge epithelia of transforming growth factor beta3-null mice, which also exhibit cleft palate. Together, these results support a role for IRF6 during the fusion events that occur during development of the lip and palate. Developmental

Multiple functions of Snail family genes during palate development in mice

“…2A-C). Similarly, the Irf6 gene, which is mutated in some human cleft palate patients and is expressed throughout the palatal shelf epithelium (Knight et al, 2006;Kondo et al, 2002), was expressed normally in Snai2 -/-and Snai1 +/-Snai2 -/-mutant embryos ( Fig. 2D-F).…”

Periderm prevents pathological epithelial adhesions during embryogenesis

“…Embryos were staged on the basis of external morphological characteristics, fixed in Bouin's solution, dehydrated through a graded ethanol series, cleared in chloroform, embedded in wax, sectioned at 6 μm, and stained with H&E. Nonradioactive section in situ hybridization was performed as described previously (48), with the exception that sections were detected using BM Purple (Roche). The Irf6 probe has been described previously (49). Detection of β-galactosidase on frozen sections was performed as described previously (50).…”

Mechanisms of tissue fusion during development

“…Indeed, insights derived from one organism have later been confirmed in mice. For example, Irf6 function in palate fusion is similar in chick and mice (Knight et al, 2006). Nonetheless, a common function is not always the case and it is important to not draw conclusions without careful analysis between animal models.…”