Expression of the Mf1 gene in developing mouse hearts: Implication in the development of human congenital heart defects

The transcription factor FKHL7 gene has recently been associated with the a nterior segment dysgenesis disorder of the eye known as Axenfeld-Rieger ano maly (ARA). A growing body of evidence indicates that mutations in FKHL7 ca use not only defects in the anterior segment of the eye but defects in the heart valves and septa as web. In order to evaluate its contribution to nor mal heart septation and valve formation, expression of the mouse homologue Mf1 in embryonic hearts was analyzed by in situ hybridization. A weak but s ignificant level of Mf1 expression could be detected in the endocardium of mouse embryos as early as day 8.5 post-conception (p.c.). Mf1 expression wa s undetectable in the hearts of day 9.5 p.c. embryos, but by day 10.5-11 p. c., Mf1 transcripts could be found again in the endocardium of both the atr ium and ventricle and a relatively strong signal was observed in the dorsal portion of the septum primum, in what appeared to be the spinal vestibule. At day 13 p.c. when aortic and pulmonary trunks are separated, relatively more Mf1 transcripts were detected in the leaflets of aortic, pulmonary, an d venous valves, the ventral portion of the septum primum, as well as in th e single layer of cells on the edges of the atrioventricular cushion tissue s. Surprisingly, there was no signal detected in the developing interventri cular septum. At day 15 p.c., overall Mf1 signals were greatly decreased. H owever, significant levels of expression could still be observed in the atr ial septum, the tricuspid valve, the mitral valve, and in the venous valve but not in the interventricular septum. The temporal and spatial expression patterns of the Mf1 gene in developing mouse hearts suggest that Mf1 may p lay a critical role in the formation of valves and septa with the exception of the interventricular septum. This is further supported by our studies s howing that mutations in the FKHL7 gene were associated with defects in the anterior segment of the eye as well as atrial septal defects or mitral val ve defects. Dev Dyn 1999;216:16-27. (C) 1999 Wiley-Liss, Inc.