BMP signaling regulates PGC numbers and motility in organ culture
BMP signaling regulates PGC numbers and motility in organ culture
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DOI：
10.1016/j.mod.2006.09.005
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Molyneaux, Kathleen
中科院分区：
文献类型：
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作者：
Dudley, Brian M.;Runyan, Chris;Molyneaux, Kathleen
骨形态发生蛋白（BMP）家族成员在多种发育过程中发挥着不同的作用。然而，在小鼠中，许多BMP、BMP受体和信号传导组分的突变导致早期胚胎死亡，使得难以分析这些因素在成人器官发生或组织稳态期间的作用。为了绕过这种早期致死性，我们使用器官培养系统来研究BMP在原始生殖细胞（PGC）迁移过程中的作用。PGCs是精子和卵子的胚胎前体。BMP诱导胚胎7.5天（E7.5）小鼠胚胎近端外胚层内原始生殖细胞的形成。PGCs然后通过肠道迁移，在E10.5到达发育中的性腺。添加BMP 4或BMP拮抗剂Noggin从E9.5胚胎解剖的横切片分别升高或降低PGC数。头蛋白治疗还减缓并随机化PGC运动，导致PGC无法定殖于泌尿生殖嵴（UGR）。基于p-Smad 1/5/8染色，迁移性PGCs对内源性BMP不应答。相反，泌尿生殖嵴的体细胞表现出升高的p-Smad 1/5/8染色，揭示了UGR内的活性BMP信号传导。头蛋白处理废除了UGR内的p-Smad染色，并阻断了Kid的局部表达，Kid是一种已知调节PGCs存活和运动的细胞因子，Id 1是一种在UGR内表达的转录因子。我们认为，BMP信号调节PGC迁移控制基因表达的体细胞内沿着迁移路线和生殖嵴内。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Members of the bone morphogenetic protein (BMP) family play diverse roles in multiple developmental processes. However, in the mouse, mutations in many BMPs, BMP receptors and signaling components result in early embryonic lethality making it difficult to analyze the role of these factors during organogenesis or tissue homeostasis in the adult. To bypass this early lethality, we used an organ culture system to study the role of BMPs during primordial germ cell (PGC) migration. PGCs are the embryonic precursors of the sperm and eggs. BMPs induce formation of primordial germ cells within the proximal epiblast of embryonic day 7.5 (E7.5) mouse embryos. PGCs then migrate via the gut to arrive at the developing gonads by E10.5. Addition of BMP4 or the BMP-antagonist Noggin to transverse slices dissected from E9.5 embryos elevated PGC numbers or reduced PGC numbers, respectively. Noggin treatment also slowed and randomized PGC movements, resulting in a failure of PGCs to colonize the urogenital ridges (UGRs). Based on p-Smad1/5/8 staining, migratory PGCs do not respond to endogenous BMPs. Instead, the somatic cells of the urogenital ridges exhibit elevated p-Smad1/5/8 staining revealing active BMP signaling within the UGRs. Noggin treatment abrogated p-Smad staining within the UGRs and blocked localized expression of Kid, a cytokine known to regulate the survival and motility of PGCs and Id1, a transcription factor expressed within the UGRs. We propose that BMP signaling regulates PGC migration by controlling gene expression within the somatic cells along the migration route and within the genital ridges. (c) 2006 Elsevier Ireland Ltd. All rights reserved.