Swiderski R E, Reiter R S, Nishimura D Y, Alward W L, Kalenak J W, Searby C S, Stone E M, Sheffield V C, Lin J J
Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242-1324, USA.
Dev Dyn. 1999 Sep;216(1):16-27. doi: 10.1002/(SICI)1097-0177(199909)216:1<16::AID-DVDY4>3.0.CO;2-1.
The transcription factor FKHL7 gene has recently been associated with the anterior segment dysgenesis disorder of the eye known as Axenfeld-Rieger anomaly (ARA). A growing 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 contribution to normal heart septation and valve formation, expression of the mouse homologue Mf1 in embryonic hearts was analyzed by in situ hybridization. A weak but significant 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 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 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, 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 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 play a critical role in the formation of valves and septa with the exception of the interventricular septum. This is further supported by our studies showing 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 valve defects. Dev Dyn 1999;216:16-27.
转录因子FKHL7基因最近被发现与眼部前段发育异常疾病阿克森费尔德-里格尔异常（ARA）有关。越来越多的证据表明，FKHL7基因突变不仅会导致眼部前段缺陷，还会导致心脏瓣膜和间隔缺陷。为了评估其对正常心脏间隔和瓣膜形成的作用，通过原位杂交分析了小鼠同源物Mf1在胚胎心脏中的表达。早在受孕后8.5天（p.c.），就可以在小鼠胚胎的心内膜中检测到微弱但显著水平的Mf1表达。在受孕后9.5天的胚胎心脏中未检测到Mf1表达，但到受孕后10.5 - 11天，Mf1转录本可再次在心房和心室的心内膜中发现，并且在原发隔的背侧部分观察到相对较强的信号，似乎是在嵴状前庭。在受孕后13天，当主动脉和肺动脉干分离时，在主动脉瓣、肺动脉瓣和静脉瓣的小叶、原发隔的腹侧部分以及房室垫组织边缘的单层细胞中检测到相对更多的Mf1转录本。令人惊讶的是，在发育中的室间隔中未检测到信号。在受孕后15天，总体Mf1信号大大降低。然而，在房间隔、三尖瓣、二尖瓣和静脉瓣中仍可观察到显著水平的表达，但在室间隔中未观察到。Mf1基因在发育中的小鼠心脏中的时空表达模式表明，Mf1可能在瓣膜和间隔（室间隔除外）的形成中起关键作用。我们的研究进一步支持了这一点，研究表明FKHL7基因突变与眼部前段缺陷以及房间隔缺损或二尖瓣缺损有关。《发育动力学》1999年；216:16 - 27。
