Phospholipase Cγ2 is necessary for separation of blood and lymphatic vasculature in mice

Phospholipase Cγ2 is necessary for separation of blood and lymphatic vasculature in mice
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DOI:
10.1242/dev.025353
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发表时间:
2009-01-15
期刊:
影响因子:
4.6
通讯作者:
Yoshida, Nobuaki
Yoshida, Nobuaki
中科院分区:
生物学2区
文献类型:
--
作者:
Ichise, Hirotake;Ichise, Taeko;Yoshida, Nobuaki

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淋巴管系统通过依赖于Prox1表达和VEGFC信号传导的机制起源于血管系统,并且以Syk和SLP76依赖性方式与血管系统分离并保持分离。然而,淋巴管与血管分离的机制尚不清楚。为了获得对血管分区的理解,我们在表现出充满血液的淋巴管的自发突变小鼠中搜索受影响的基因,并通过定位候选克隆鉴定了编码磷脂酶C γ 2(PLC γ 2)的Plcg 2基因的无效突变。在PLC γ 2缺失小鼠中观察到的血淋巴分流是由于血管和淋巴管的异常分离。在用PLC γ 2缺失骨髓细胞重建的致死性辐照野生型小鼠中观察到类似的表型。这些发现表明PLC γ 2在启动和维持血液和淋巴管系统的分离中起着重要作用。
The lymphatic vasculature originates from the blood vasculature through a mechanism relying on Prox1 expression and VEGFC signalling, and is separated and kept separate from the blood vasculature in a Syk- and SLP76-dependent manner. However, the mechanism by which lymphatic vessels are separated from blood vessels is not known. To gain an understanding of the vascular partitioning, we searched for the affected gene in a spontaneous mouse mutant exhibiting blood-filled lymphatic vessels, and identified a null mutation of the Plcg2 gene, which encodes phospholipase C gamma 2 (PLC gamma 2), by positional candidate cloning. The blood-lymph shunt observed in PLC gamma 2-null mice was due to aberrant separation of blood and lymphatic vessels. A similar phenotype was observed in lethally irradiated wild-type mice reconstituted with PLC gamma 2-null bone marrow cells. These findings indicate that PLC gamma 2 plays an essential role in initiating and maintaining the separation of the blood and lymphatic vasculature.