MAPK1 is required for establishing the pattern of cell proliferation and for cell survival during lens development
MAPK1 is required for establishing the pattern of cell proliferation and for cell survival during lens development
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DOI：
10.1242/dev.081042
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发表时间：
2013-04-01
期刊：
影响因子：
4.6
通讯作者：
Reneker, Lixing W.
中科院分区：
文献类型：
--
作者：
Upadhya, Dinesh;Ogata, Masato;Reneker, Lixing W.
丝裂原活化蛋白激酶（MAPK;也称为ERK）是在组织中广泛表达的关键细胞内信号传导分子，并且被认为是功能等同的。在这里，我们使用小鼠透镜作为模型系统，调查是否MAPK 1在发展过程中发挥了特定的作用。已知MAPK 3在透镜开发中是可降解的。我们证明，虽然MAPK 1是均匀地表达在透镜上皮细胞，其删除显着减少细胞增殖的周边地区，一个地区被称为透镜萌发区，其中最活跃的细胞分裂发生在正常的透镜发展。相比之下，中心区域的细胞增殖受MAPK 1缺失的影响最小。细胞周期调节因子，包括细胞周期蛋白D1和生存素，在MAPK 1缺陷型透镜的萌发区下调。有趣的是，MAPK 1的丢失随后诱导透镜上皮中磷酸化MAPK 3（pMAPK 3）水平的上调;然而，pMAPK 3的这种增加不足以恢复萌发区中的细胞增殖。此外，MAPK 1在上皮细胞存活中起重要作用，但在透镜发育期间对纤维细胞分化不利。我们的数据表明，MAPK 1/3控制细胞增殖的透镜上皮细胞在空间上定义的方式，MAPK 1起着独特的作用，在建立高度有丝分裂区的周边地区，而两个MAPKs共享一个冗余的作用，在控制细胞增殖的中央区域的透镜上皮。
The mitogen-activated protein kinases (MAPKs; also known as ERKs) are key intracellular signaling molecules that are ubiquitously expressed in tissues and were assumed to be functionally equivalent. Here, we use the mouse lens as a model system to investigate whether MAPK1 plays a specific role during development. MAPK3 is known to be dispensable for lens development. We demonstrate that, although MAPK1 is uniformly expressed in the lens epithelium, its deletion significantly reduces cell proliferation in the peripheral region, an area referred to as the lens germinative zone in which most active cell division occurs during normal lens development. By contrast, cell proliferation in the central region is minimally affected by MAPK1 deletion. Cell cycle regulators, including cyclin D1 and survivin, are downregulated in the germinative zone of the MAPK1-deficient lens. Interestingly, loss of MAPK1 subsequently induces upregulation of phosphorylated MAPK3 (pMAPK3) levels in the lens epithelium; however, this increase in pMAPK3 is not sufficient to restore cell proliferation in the germinative zone. Additionally, MAPK1 plays an essential role in epithelial cell survival but is dispensable for fiber cell differentiation during lens development. Our data indicate that MAPK1/3 control cell proliferation in the lens epithelium in a spatially defined manner; MAPK1 plays a unique role in establishing the highly mitotic zone in the peripheral region, whereas the two MAPKs share a redundant role in controlling cell proliferation in the central region of the lens epithelium.