Ventral closure, headfold fusion and definitive endoderm migration defects in mouse embryos lacking the fibronectin leucine-rich transmembrane protein FLRT3
Ventral closure, headfold fusion and definitive endoderm migration defects in mouse embryos lacking the fibronectin leucine-rich transmembrane protein FLRT3
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DOI：
10.1016/j.ydbio.2008.03.021
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发表时间：
2008-06-01
影响因子：
2.7
通讯作者：
Robertson, Elizabeth J.
中科院分区：
文献类型：
--
作者：
Maretto, Silvia;Mueller, Pari-Sima;Robertson, Elizabeth J.
这三种富含亮氨酸重复序列的跨膜蛋白包括10个富亮氨酸重复序列(LRR)、一个III型纤维连接蛋白(FN)结构域、紧随其后的跨膜区和一条短的细胞质尾巴。XFlr3是一个Nodal/转化生长因子β靶标，在非洲爪哇原肠发育过程中调节细胞黏附和调节成纤维细胞生长因子信号。本研究描述了Flrt1-3在小鼠早期胚胎中表达的开始和模式。Flrt3的表达在前内脏内胚层(AVE)中被激活，在原肠形成过程中出现在前条纹的衍生体，即结节、脊索和新出现的最终内胚层。为了探索Flrt3的功能，我们通过基因打靶产生了一个空等位基因。前-后(A-P)构型、原始条纹形成和左-右(L-R)轴确定所需的早期结节活动未受干扰。然而，Flrt3突变胚胎在头褶融合、明确的内胚层迁移和腹侧体壁侧缘融合失败方面表现出缺陷，导致贲门裂。令人惊讶的是，突变对成纤维细胞生长因子信号没有影响。总之，这些实验表明，在发育中的小鼠胚胎中，Flrt3在控制细胞黏附和组织形态发生方面发挥着关键作用。(C)2008 Elsevier Inc.保留所有权利。
The three fibronectin leucine-rich repeat transmembrane (FLRT) proteins contain 10 leucine-rich repeats (LRR), a type III fibronectin (FN) domain, followed by the transmembrane region, and a short cytoplasmic tail. XFLRT3, a Nodal/TGF beta target, regulates cell adhesion and modulates FGF signalling during Xenopus gastrulation. The present study describes the onset and pattern of FLRT1-3 expression in the early mouse embryo. FLRT3 expression is activated in the anterior visceral endoderm (AVE), and during gastrulation appears in anterior streak derivatives namely the node, notochord and the emerging definitive endoderm. To explore FLRT3 function we generated a null allele via gene targeting. Early Nodal activities required for anterior-posterior (A-P) patterning, primitive streak formation and left-right (L-R) axis determination were unperturbed. However, FLRT3 mutant embryos display defects in headfold fusion, definitive endoderm migration and a failure of the lateral edges of the ventral body wall to fuse, leading to cardia bifida. Surprisingly, the mutation has no effect on FGF signalling. Collectively these experiments demonstrate that FLRT3 plays a key role in controlling cell adhesion and tissue morphogenesis in the developing mouse embryo. (C) 2008 Elsevier Inc. All rights reserved.