Expression of the vertebrate Slit gene family and their putative receptors, the Robo genes, in the developing murine kidney

Expression of the vertebrate Slit gene family and their putative receptors, the Robo genes, in the developing murine kidney
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DOI:
10.1016/s0925-4773(00)00313-0
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发表时间:
2000-06-01
影响因子:
2.6
通讯作者:
Little, M
Little, M
中科院分区:
生物学4区
文献类型:
--
作者:
Piper, M;Georgas, K;Little, M

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编码分泌糖蛋白的slit(sli)基因已被证明通过作为长袍受体的信号配体在黑腹果蝇(Drosophila melanogaster)的轴突导向中起重要作用(Rothberg,J.M.,雅各布斯,J.R.,古德曼,C.S.,Artavanis-Tsakonas,S.,1990.狭缝:中线神经胶质细胞和连合轴突通路发育所必需的细胞外蛋白,含有EGF和LRR结构域。Genes Dev. 4,2169-2187; Kidd,T.,Bland,K.S.,古德曼,C.S.,1999. Slit是果蝇中robo受体的中线驱避剂。Cell 96,785-794)。已经在脊椎动物中鉴定了sli和长袍的多种同源物,并且认为它们在神经发育中与它们的果蝇对应物起类似的作用(Brose,K.,Bland,K.S.,Wang,K.H.,阿诺特,D.,Henzel,W.,古德曼,C.S.,Tessier-Lavigne,M.,基德,T.,1999. Slit蛋白结合长袍受体,并在排斥性轴突引导中具有进化上保守的作用。Cell 96,795-806)。已显示Slit 2结合Robo 1,介导发育中的中枢神经系统(CNS)中的神经元和轴突引导(Brose等人,1999; Hu,H.,1999.哺乳动物前脑发育中Slit 2对神经元迁移的化学排斥作用Neuron 23,703-711)。重要的是,两个基因家族在CNS外显示出不同的表达模式(Holmes,G. P.,Negus,K.,伯里奇湖拉曼,S.,Algar,E.,山田,T.,Little,M.H.,1998.两种脊椎动物狭缝同源物的不同但重叠的表达模式意味着在中枢神经系统发育和器官发生中的功能作用。机械设备79,57-72; Yuan,W.,Zhou,L.,中国科学院,陈建辉吴,J.Y.,拉奥,Y.,Ornitz,D. M.,1999.小鼠SLIT家族:ROBO的分泌配体表达模式表明其在形态发生和轴突引导中的作用。Dev. 212,290-306)。采用原位杂交技术,对小鼠后肾组织培养和泌尿生殖道切片进行原位杂交,研究Slit 1、2、3和Robo 1和2在小鼠后肾发育过程中的表达模式。Slit 1在输尿管树周围的后肾间充质中表达。Slit 2在UT的尖端表达,Slit 2和Slid均在逗号形和S形体的远近端表达。Robo 1的表达最初弥漫在整个MM中,然后在pretubular聚集体中上调,并保持在逗号和S形小体的远端。Robo 2在树枝状UT尖端周围的诱导MM中检测到,随后在S形主体的近端检测到。在后肾发育过程中,Robo 1和Slit 1在后肾间充质中同时表达,Robo 2、Slit 2和Slid在S形小体远端同时表达。(C)2000爱思唯尔科学爱尔兰有限公司保留所有权利。
The slit (sli) gene, encoding a secreted glycoprotein, has been demonstrated to play a vital role in axonal guidance in Drosophila melanogaster by acting as a signalling ligand for the robe receptor (Rothberg, J.M., Jacobs, J.R., Goodman, C.S., Artavanis-Tsakonas, S., 1990. slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains. Genes Dev. 4, 2169-2187; Kidd, T., Bland, K.S., Goodman, C.S., 1999. Slit is the midline repellent for the robo receptor in Drosophila. Cell 96, 785-794). Multiple homologs of both sli and robe have been identified in vertebrates and are thought to play similar roles to their fly counterparts in neural development (Brose, K., Bland, K.S., Wang, K.H., Arnott, D., Henzel, W., Goodman, C.S., Tessier-Lavigne, M., Kidd, T., 1999. Slit proteins bind Robe receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96, 795-806). Slit2 has been shown to bind Robo1, mediating both neuronal and axonal guidance in the developing central nervous system (CNS), (Brose et al., 1999; Hu, H., 1999. Chemorepulsion of neuronal migration by Slit2 in the developing mammalian forebrain. Neuron 23, 703-711). Importantly, both gene families display distinct expression patterns outside the CNS (Holmes, G.P., Negus, K., Burridge, L., Raman, S., Algar, E., Yamada, T., Little, M.H., 1998. Distinct but overlapping expression patterns of two vertebrate slit homologs implies functional roles in CNS development and organogenesis. Mech. Dev. 79, 57-72; Yuan, W., Zhou, L., Chen, J.H., Wu, J.Y., Rao, Y., Ornitz, D.M., 1999. The mouse SLIT family: secreted ligands for ROBO expressed in patterns that suggest a role in morphogenesis and axon guidance. Dev. Biol. 212, 290-306). Using in situ hybridization on metanephric explant cultures and urogenital tract sections, the expression patterns of Slit1, 2, 3 and Robo1 and 2 were investigated during murine metanephric development. Slit1 was expressed in the metanephric mesenchyme (MM) surrounding the invading ureteric tree (UT). Slit2 was expressed at the tips of the UT and both Slit2 and Slid were expressed at the far proximal end of the comma shaped and S-shaped bodies. Expression of Robo1 was initially diffuse throughout the MM, then upregulated in the pretubular aggregates, and maintained at the distal end of the comma and S-shaped bodies. Robo2 was detected in the induced MM surrounding the arborizing UT tips and later in the proximal end of the S-shaped bodies. Coincident expression of Robo1 with Slit1 in the metanephric mesenchyme and Robo2, Slit2 and Slid in the far proximal end of the S-shaped bodies was observed during metanephric development. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.