Expression of theMf1 gene in developing mouse hearts: Implication in the development of human congenital heart defects

Autor: Charles S. Searby, Wallace L.M. Alward, Ruth E. Swiderski, Val C. Sheffield, Edwin M. Stone, Darryl Y. Nishimura, Rebecca S. Reiter, Jeffrey W. Kalenak, Jim J.-C. Lin
Rok vydání: 1999
Předmět:
Zdroj: Developmental Dynamics. 216:16-27
ISSN: 1097-0177
1058-8388
Popis: The transcription factor FKHL7 gene has recently been associated with the ante- rior segment dysgenesis disorder of the eye known as Axenfeld-Rieger anomaly (ARA). A grow- ing body of evidence indicates that mutations in FKHL7 cause not only defects in the anterior segment of the eye but defects in the heart valves and septa as well. In order to evaluate its contri- bution to normal heart septation and valve forma- tion, expression of the mouse homologue Mf1 in embryonic hearts was analyzed by in situ hybrid- ization. A weak but significant level of Mf1 expres- sion could be detected in the endocardium of mouse embryos as early as day 8.5 post-concep- tion (p.c.). Mf1 expression was 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 atrium and ven- tricle 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, and venous valves, the ventral portion of the septum primum, as well as in the single layer of cells on the edges of the atrioventricular cushion tissues. Surprisingly, there was no signal detected in the developing interventricular septum. At day 15 p.c., overall Mf1 signals were greatly decreased. However, significant levels of expression could still be observed in the atrial septum, the tricus- pid 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 play a critical role in the formation of valves and septa with the exception of the inter- ventricular septum. This is further supported by our studies showing that mutations in the FKHL7 gene were associated with defects in the anterior
Databáze: OpenAIRE
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