Crosstalk between the p 1 90-B RhoGAP and lGF signaling pathways is required for embryonic mammary bud development
Crosstalk between the p 1 90-B RhoGAP and lGF signaling pathways is required for embryonic mammary bud development
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DOI：
10.1016/j.ydbio.2007.07.002
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发表时间：
2007-09-01
影响因子：
2.7
通讯作者：
Rosen, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Heckman, Brandy M.;Chakravarty, Geetika;Rosen, Jeffrey M.
P190-B RhoGAP(P190-B，又称ARHGAP5)在乳腺导管形态发生过程中，在末端芽(TEB)侵入周围脂肪垫中起重要作用。在这里，我们报告了纯合子p190-B基因缺失的胚胎在胚胎乳房芽发育中表现出主要的缺陷。总体而言，p190-B缺失的芽体积较小，细胞较少，表现出间充质增殖和分化受损的特征。与已报道的p190-B缺失对IGF-1R信号的影响一致，IGF-1R缺陷的胚胎也表现出类似的小乳芽表型。然而，与p190-B缺陷的胚胎不同，IGF-1R缺陷的胚胎表现出上皮细胞增殖减少，并且没有间质缺陷。由于IGF和p190-B信号都影响IRS-1/2，我们研究了IRS-1/2双敲除胚胎乳房芽。这些胚胎表现出与p190-B缺陷胚胎相似的主要缺陷，包括较小的芽大小。重要的是，与p190-B缺陷的芽一样，IRS-1/2缺陷的间充质的增殖也受到了抑制。这些结果表明，IGF通过p190-B和IRS蛋白对乳房芽形成以及维持乳房芽形态发生所必需的上皮-间充质相互作用至关重要。(C)2007 Elsevier Inc.保留所有权利。
P 190-B RhoGAP (p 190-B, also known as ARHGAP5) has been shown to play an essential role in invasion of the terminal end buds (TEBs) into the surrounding fat pad during mammary gland ductal morphogenesis. Here we report that embryos with a homozygous p 190-B gene deletion exhibit major defects in embryonic mammary bud development. Overall, p 190-B-deficient buds were smaller in size, contained fewer cells, and displayed characteristics of impaired mesenchymal proliferation and differentiation. Consistent with the reported effects of p190-B deletion on IGF-1R signaling, IGF-1R-deficient embryos also displayed a similar small mammary bud phenotype. However, unlike the p 190-B-deficient embryos, the IGF-1R-deficient embryos exhibited decreased epithelial proliferation and did not display mesenchymal defects. Because both IGF and p190-B signaling affect IRS-1/2, we examined IRS-1/2 double knockout embryonic mammary buds. These embryos displayed major defects similar to the p190-B-deficient embryos including smaller bud size. Importantly, like the p190-B-deficient buds, proliferation of the IRS-1/2-deficient mesenchyme was impaired. These results indicate that IGF signaling through p190-B and IRS proteins is critical for mammary bud formation and ensuing epithelial-mesenchymal interactions necessary to sustain mammary bud morphogenesis. (c) 2007 Elsevier Inc. All rights reserved.