Requirement of DLG1 for cardiovascular development and tissue elongation during cochlear, enteric, and skeletal development: possible role in convergent extension.
Requirement of DLG1 for cardiovascular development and tissue elongation during cochlear, enteric, and skeletal development: possible role in convergent extension.
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DOI：
10.1371/journal.pone.0123965
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Matsuzaki T
中科院分区：
文献类型：
--
作者：
Iizuka-Kogo A;Senda T;Akiyama T;Shimomura A;Nomura R;Hasegawa Y;Yamamura K;Kogo H;Sawai N;Matsuzaki T
Dlg 1基因编码参与上皮细胞极化的MAGUK蛋白家族成员。Dlg 1基因突变小鼠（Dlg 1-/-小鼠）表现出呼吸衰竭和发绀，出生后不久死亡。然而，这种新生儿死亡的原因尚未确定。在本研究中，我们进一步检查了Dlg 1-/-小鼠，发现心血管系统的严重缺陷，包括室间隔缺损，持续动脉干，右心室双出口，这将导致新生儿死亡。这些心血管表型类似于缺乏平面细胞极性（PCP）基因的突变小鼠，并支持最近的概念，即DLG 1参与PCP途径。我们评估了DLG 1在其他器官发育中的参与程度，如耳蜗，肠和骨骼，其中PCP信号传导被认为发挥了作用。在Corti器中，组织伸长受到抑制，伴随着毛细胞行的无序排列，而静纤毛束的方向是正常的。在胸骨中，观察到胸骨裂、软骨的异常钙化模式和软骨细胞的紊乱。此外，观察到肠、胸骨和四肢长骨缩短。Dlg 1-/-小鼠的这些表型涉及细胞解体和组织伸长不足，强烈表明这些小鼠的会聚性伸展运动存在缺陷。因此，我们目前的研究结果提供了一种可能性，DLG 1是特别需要的PCP信号依赖的过程之间的收敛扩展。
The Dlg1 gene encodes a member of the MAGUK protein family involved in the polarization of epithelial cells. Null mutant mice for the Dlg1 gene (Dlg1-/- mice) exhibit respiratory failure and cyanosis, and die soon after birth. However, the cause of this neonatal lethality has not been determined. In the present study, we further examined Dlg1-/- mice and found severe defects in the cardiovascular system, including ventricular septal defect, persistent truncus arteriosus, and double outlet right ventricle, which would cause the neonatal lethality. These cardiovascular phenotypes resemble those of mutant mice lacking planar cell polarity (PCP) genes and support a recent notion that DLG1 is involved in the PCP pathway. We assessed the degree of involvement of DLG1 in the development of other organs, as the cochlea, intestine, and skeleton, in which PCP signaling has been suggested to play a role. In the organ of Corti, tissue elongation was inhibited accompanied by disorganized arrangement of the hair cell rows, while the orientation of the stereocilia bundle was normal. In the sternum, cleft sternum, abnormal calcification pattern of cartilage, and disorganization of chondrocytes were observed. Furthermore, shortening of the intestine, sternum, and long bones of the limbs was observed. These phenotypes of Dlg1-/- mice involving cellular disorganization and insufficient tissue elongation strongly suggest a defect in the convergent extension movements in these mice. Thus, our present results provide a possibility that DLG1 is particularly required for convergent extension among PCP signaling-dependent processes.
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影响因子：
56.9
作者：
Matsumine, A;Ogai, A;Akiyama, T
通讯作者：
Akiyama, T
影响因子：
64.8
作者：
Lu, XW;Borchers, AGM;Tessier-Lavigne, M
通讯作者：
Tessier-Lavigne, M
影响因子：
--
作者：
Kawakami, Minoru;Umeda, Masafumi;Yamamura, Ken-ichi
通讯作者：
Yamamura, Ken-ichi
DOI：
10.1002/bdrc.20013
发表时间：
2004-06-01
期刊：
Birth defects research. Part C, Embryo today : reviews
影响因子：
--
作者：
Farlie, Peter G;McKeown, Sonja J;Newgreen, Donald F
通讯作者：
Newgreen, Donald F
影响因子：
20.1
作者：
Henderson, DJ;Conway, SJ;Copp, AJ
通讯作者：
Copp, AJ