Bone Morphogenetic Proteins Inhibit Ciliogenesis of Ependymal Cells in Vitro.
Bone Morphogenetic Proteins Inhibit Ciliogenesis of Ependymal Cells in Vitro.
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骨形态发生蛋白在体外抑制室管膜细胞纤毛发生。
DOI：
10.1620/tjem.252.199
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
N. Osumi
中科院分区：
文献类型：
--
作者：
K. Hiraoka;H. Inada;K. Yanai;N. Osumi
室管膜细胞通过其多个纤毛的运动在调节脑脊液流动的动力学中具有重要作用。纤毛的产生或功能受损可由于脑脊液流动的动力学紊乱而引起脑积水。然而，调节室管膜细胞分化及其纤毛发生的分子基础尚未完全阐明。我们在这里报告，骨形态发生蛋白（BMP），生长因子协调整个身体的组织结构，抑制纤毛发生室管膜细胞分化在原代细胞培养。已有研究表明Smad 6和Smad 7的异位表达可促进胚胎干细胞向多纤毛室管膜样细胞的分化。由于Smad 6和Smad 7已被认为是BMP信号通路的细胞内抑制因子，因此该通路的激活可导致室管膜细胞纤毛发生的缺陷。为了检查通路的激活是否影响纤毛发生，我们研究了两种BMPs，BMP 2和BMP 4，对从新生小鼠脑制备的原代培养细胞的室管膜分化的影响。在培养基中补充BMP 2或BMP 4显著减少了总细胞中具有多个纤毛的细胞的数量，而大多数细胞表达FoxJ 1，这是纤毛发生的主要调节因子。通过BMP受体下游因子细胞内Smad 1/5/8的磷酸化证实了该通路的激活。这些体外结果表明，在体内室管膜细胞分化期间，抑制BMP信号通路可能对纤毛发生至关重要。
Ependymal cells have an essential role in regulating the dynamics of the cerebrospinal fluid flow by the movement of their multiple cilia. Impaired generation or function of cilia could cause hydrocephalus due to the disordered dynamics of the cerebrospinal fluid flow. However, molecular bases regulating differentiation of the ependymal cells and their ciliogenesis have not been fully elucidated. We report here that bone morphogenetic proteins (BMPs), growth factors orchestrating tissue architecture throughout the body, inhibit ciliogenesis during ependymal cell differentiation in primary cell culture. Previous in vitro study has reported that ectopic expression of Smad6 and Smad7 promotes differentiation of embryonic stem cells into multi-ciliated ependymal-like cells. Since Smad6 and Smad7 have been known as the intracellular inhibitory factors of the BMP signaling pathway, the activation of the pathway could cause a deficit in ciliogenesis of ependymal cells. To examine whether activation of the pathway affects ciliogenesis, we investigated the effects of two BMPs, BMP2 and BMP4, on the ependymal differentiation of the primary cultured cells prepared from the neonatal mouse brain. Supplementation of BMP2 or BMP4 in culture media significantly reduced the number of cells with multiple cilia among the total cells, while most of the cells expressed FoxJ1, a master regulator of ciliogenesis. Activation of the pathway was confirmed by the phosphorylation of intracellular Smad1/5/8, downstream factors of the BMP receptors. These in vitro results suggest that inhibition of the BMP signaling pathway might be essential for ciliogenesis during the ependymal cell differentiation in vivo.