Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis.
Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis.
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DOI：
10.1186/1471-213x-7-55
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发表时间：
2007-05-22
影响因子：
--
通讯作者：
Tamagnone L
中科院分区：
文献类型：
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作者：
Fazzari P;Penachioni J;Gianola S;Rossi F;Eickholt BJ;Maina F;Alexopoulou L;Sottile A;Comoglio PM;Flavell RA;Tamagnone L
丛蛋白是脑信号蛋白的跨膜受体的大家族，已知其在神经回路的组装中的作用。最近，丛状蛋白已涉及多种生物功能，包括血管生长，上皮组织形态发生和肿瘤的发展。特别是，PlexinB1，Sema4D的受体，已被建议在神经发育和肿瘤血管生成中发挥作用，基于体外研究。然而，丛蛋白B1的组织分布尚未得到广泛研究，该受体在体内的功能相关性仍有待实验测试。为了阐明丛蛋白B1在体内的功能，我们因此进行了小鼠基因的基因组靶向，以获得功能缺失突变体。这项研究表明，丛蛋白B1受体和它的假定配体，Sema4D，有一个选择性分布在神经和上皮组织在发展过程中，并在成人。丛蛋白B1和Sema4D在组织中显示出很大程度上互补的细胞分布，这与丛蛋白B1在体内充当Sema4D受体的想法一致。有趣的是，丛蛋白B1也表达在某些组织中的Sema4D的情况下，这表明Sema4D独立的活动。PlexinB1在肺、肾、肝和小脑中有高表达。缺乏脑信号蛋白受体丛蛋白B1表达的突变小鼠是可行的和可生育的。虽然Sema4D的轴突塌陷活动在丛蛋白B1缺陷神经元中受损，但我们无法检测到发育中的主要缺陷，或表达丛蛋白B1的组织的成人组织学和基本功能参数。此外，在没有丛蛋白B1的情况下，原位植入的肿瘤诱导的血管生成反应不受影响，表明这种脑信号蛋白受体在内皮细胞中的表达是多余的。我们的表达分析表明，丛蛋白B1在小鼠发育和组织稳态在成人多方面的作用。尽管如此，丛蛋白B1的基因缺失不会导致重大的发育缺陷或明显的功能异常。我们推断丛蛋白B1在小鼠发育中起着多余的作用，并且它不是肿瘤诱导的血管生成所严格需要的。
Plexins are a large family of transmembrane receptors for the Semaphorins, known for their role in the assembly of neural circuitry. More recently, Plexins have been implicated in diverse biological functions, including vascular growth, epithelial tissue morphogenesis and tumour development. In particular, PlexinB1, the receptor for Sema4D, has been suggested to play a role in neural development and in tumour angiogenesis, based on in vitro studies. However, the tissue distribution of PlexinB1 has not been extensively studied and the functional relevance of this receptor in vivo still awaits experimental testing. In order to shed light on PlexinB1 function in vivo, we therefore undertook the genomic targeting of the mouse gene to obtain loss of function mutants. This study shows that PlexinB1 receptor and its putative ligand, Sema4D, have a selective distribution in nervous and epithelial tissues during development and in the adult. PlexinB1 and Sema4D show largely complementary cell distribution in tissues, consistent with the idea that PlexinB1 acts as the receptor for Sema4D in vivo. Interestingly, PlexinB1 is also expressed in certain tissues in the absence of Sema4D, suggesting Sema4D independent activities. High expression of PlexinB1 was found in lung, kidney, liver and cerebellum. Mutant mice lacking expression of semaphorin receptor PlexinB1 are viable and fertile. Although the axon collapsing activity of Sema4D is impaired in PlexinB1 deficient neurons, we could not detect major defects in development, or in adult histology and basic functional parameters of tissues expressing PlexinB1. Moreover, in the absence of PlexinB1 the angiogenic response induced by orthotopically implanted tumours was not affected, suggesting that the expression of this semaphorin receptor in endothelial cells is redundant. Our expression analysis suggests a multifaceted role of PlexinB1 during mouse development and tissue homeostasis in the adult. Nonetheless, the genetic deletion of PlexinB1 does not result in major developmental defects or clear functional abnormalities. We infer that PlexinB1 plays a redundant role in mouse development and it is not strictly required for tumour induced angiogenesis.