The mouse mammary gland requires the actin-binding protein gelsolin for proper ductal morphogenesis
The mouse mammary gland requires the actin-binding protein gelsolin for proper ductal morphogenesis
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DOI：
10.1006/dbio.2000.9844
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发表时间：
2000-09-15
影响因子：
2.7
通讯作者：
Asch, BB
中科院分区：
文献类型：
--
作者：
Crowley, MR;Head, KL;Asch, BB
凝溶胶蛋白是一种肌动蛋白结合/切割蛋白，以细胞内和分泌形式表达。它是大多数细胞中肌动蛋白细胞骨架的形式和功能的主要调节剂。在这里，我们证明了有针对性的删除凝溶胶蛋白基因（GSN-/-）的雌性小鼠有缺陷的乳腺形态发生。在无凝溶胶蛋白的乳腺中发现了两个明显的缺陷。首先，来自Gsn-/-小鼠的乳腺原基在青春期开始时未能伸长，并且保持基本直到约9周龄，早期阻滞（Gsn-/-（EB））。其次，在乳腺上皮填充乳腺脂肪垫后，观察到完全缺乏终末分支或晚期阻滞（Gsn-/-（LB））。在70%的Gsn-/-小鼠中观察到Gsn-/-（EB），并且似乎除了凝溶胶蛋白的损失之外还依赖于修饰基因。在所有Gsn-/-小鼠中观察到Gsn-/-（LB）。在Gsn-/-（EB）小鼠的乳腺原基中，直到大约9周龄时，末端芽（TEB）才明显。溴脱氧尿苷掺入法检测到GSN-/-（EB）女性末端导管区域的细胞增殖，但低于年龄匹配的对照组TEBs中发现的细胞增殖。在缺乏凝溶胶蛋白的小鼠中，乳腺结构在组织学水平上没有改变。小叶肺泡发育延迟响应妊娠Gsn-/-小鼠乳腺，但在其他方面是正常的。无凝溶胶蛋白动物的泌乳和退化与野生型小鼠相似。移植的上皮细胞缺乏凝溶胶蛋白到野生型（GsnWT）乳腺脂肪垫导致适当的树枝状的导管树。将GsnWT上皮移植到Gsn-/-脂肪垫中重现了在Gsn-/-雌性中观察到的末端分支的缺乏。这些结果表明，凝溶胶蛋白是必要的乳腺基质适当的导管形态发生。我们的研究结果提供了第一个证据，肌动蛋白调节蛋白影响乳腺导管的生长，通过基质上皮通讯。(C)北京大学出版社.
Gelsolin is an actin-binding/severing protein expressed in intracellular and secreted forms. It is a major regulator of the form and function of the actin cytoskeleton in most all cells. Here we demonstrate that female mice with a targeted deletion of the gelsolin gene (Gsn-/-) have defects in mammary gland morphogenesis. Two distinct defects were identified in the gelsolin-null mammary gland. First, the mammary anlage from Gsn-/- mice failed to elongate at the onset of puberty and remained rudimentary until approximately 9 weeks of age, early block (Gsn-/-(EB)). Second, after the mammary epithelium had filled the mammary fat pad, a complete lack of terminal branching, or late block, was observed (Gsn-/-(LB)). The Gsn-/-(EB) was seen in 70% of Gsn-/- mice and appeared to be dependent on a modifier gene(s) in addition to the loss of gelsolin. Gsn-/-(LB) was observed in all Gsn-/- mice. Terminal end buds (TEBs) were not evident in the mammary anlage from Gsn-/-(EB) mice until approximately 9 weeks of age. Cellular proliferation in the terminal ductal regions of Gsn-/-(EB) females was detected by bromodeoxyuridine incorporation, but was less than that found in the TEBs of age-matched controls. In mice deficient for gelsolin, mammary gland architecture was unaltered at the histological level. Lobuloalveolar development was delayed in response to pregnancy in mammary glands of Gsn-/- mice but was otherwise normal. Lactation and involution in the gelsolin-null animals were similar to those of wild-type mice. Transplantation of epithelium devoid of gelsolin into a wild-type (GsnWT) mammary fat pad resulted in proper arborization of the ductal tree. Transplantation of GsnWT epithelium into the Gsn-/- fat pad recapitulated the lack of terminal branching seen in Gsn-/- females. These results indicate that gelsolin is required in the mammary stroma for proper ductal morphogenesis. Our results provide the first evidence of an actin regulatory protein affecting mammary ductal growth through stromal-epithelial communication. (C) 2000 Academic Press.