Ott Elisabeth B, van den Akker Nynke M S, Sakalis Philippe A, Gittenberger-de Groot Adriana C, Te Velthuis Aartjan J W, Bagowski Christoph P
Institute of Biology, Department of Molecular and Cellular Biology, University of Leiden, Leiden, The Netherlands.
Dev Dyn. 2008 Dec;237(12):3940-52. doi: 10.1002/dvdy.21807.
The LIM domain only protein 7 (LMO7), a member of the PDZ and LIM domain-containing protein family is a candidate gene with possible roles in embryonic development and breast cancer progression. LMO7 has been linked to actin cytoskeleton organization through nectin/afadin and to cell-cell adhesion by means of E-cadherin/catenin. In addition, LMO7 has been shown to regulate transcription of the nuclear membrane protein Emerin and other muscle relevant genes. In this study, we used in situ hybridization to investigate LMO7 expression during embryonic development in three widely used vertebrate model species: the zebrafish, the chicken and the mouse. Our temporal and spatial gene expression analysis revealed both common and distinct patterns between these species. In mouse and chicken embryos we found expression in the outflow tract, the inflow tract, the pro-epicardial organ and the second heart field, structures highly important in the developing heart. Furthermore, gene knockdown experiments in zebrafish embryos resulted in severe defects in heart development with effects on the conduction system and on heart localization. In summary, we present here the first developmental study of LMO7. We reveal the temporal and spatial expression patterns of this important gene during mouse, chicken and fish development and our findings suggest essential functions for LMO7 during vertebrate heart development.
仅含LIM结构域蛋白7(LMO7)是含PDZ和LIM结构域蛋白家族的成员,是一个候选基因,可能在胚胎发育和乳腺癌进展中发挥作用。LMO7已通过nectin/afadin与肌动蛋白细胞骨架组织相关联,并通过E-钙黏蛋白/连环蛋白与细胞间黏附相关。此外,LMO7已被证明可调节核膜蛋白Emerin和其他肌肉相关基因的转录。在本研究中,我们使用原位杂交技术研究了LMO7在三种广泛使用的脊椎动物模型物种(斑马鱼、鸡和小鼠)胚胎发育过程中的表达情况。我们的时空基因表达分析揭示了这些物种之间既有共同的表达模式,也有不同的表达模式。在小鼠和鸡胚胎中,我们发现LMO7在流出道、流入道、心外膜前体器官和第二心脏场中表达,这些结构在心脏发育中非常重要。此外,斑马鱼胚胎中的基因敲低实验导致心脏发育出现严重缺陷,对传导系统和心脏定位产生影响。总之,我们在此展示了对LMO7的首次发育研究。我们揭示了该重要基因在小鼠、鸡和鱼类发育过程中的时空表达模式,我们的研究结果表明LMO7在脊椎动物心脏发育过程中具有重要功能。