Expression profiles of cIRF6, cLHX6 and cLHX7 in the facial primordia suggest specific roles during primary palatogenesis.

BACKGROUND: The LIM-homeodomain transcription factors LHX7 and LHX6 have been implicated in palatogenesis in mice and thus may also contribute to the incidence of isolated palatal clefts and/or clefts of the lip and primary palate (CL/P) in humans. Causative mutations in the transcription factor IRF6 have also been identified in two allelic CL/P syndromes and common polymorphisms in the same gene are significantly associated with non-syndromal CL/P in different populations. RESULTS: Here we report the isolation of chick orthologues of LHX7, LHX6 and IRF6 and the first characterisation of their profiles of expression during morphogenesis of the midface with emphasis on the period around formation of the primary palate. LHX7 and LHX6 expression was restricted to the ectomesenchyme immediately underlying the ectoderm of the maxillary and mandibular primordia as well as to the lateral globular projections of the medial nasal process, again underlying the pre-fusion primary palatal epithelia. In contrast, IRF6 expression was restricted to surface epithelia, with elevated levels around the frontonasal process, the maxillary primordia, and the nasal pits. Elsewhere, high expression was also evident in the egg tooth primordium and in the apical ectodermal ridge of the developing limbs. CONCLUSION: The restricted expression of both LHX genes and IRF6 in the facial primordia suggests roles for these gene products in promoting directed outgrowth and fusion of the primary palate. The manipulability, minimal cost and susceptibility of chicks to CL/P will enable more detailed investigations into how perturbations of IRF6, LHX6 and LHX7 contribute to common orofacial clefts.