The transparent and refractive properties of the ocular lens are dependent on its precise cellular structure, supported by the regulation of lens cellular processes of proliferation and differentiation that are essential throughout life. The ERK/MAPK-signalling pathway plays a crucial role in regulating lens cell proliferation and differentiation, and in turn is regulated by inhibitory molecules including the Spred family of proteins to modulate and attenuate the impact of growth factor stimulation. Given Spreds are strongly and distinctly expressed in lens, along with their established inhibitory role in a range of different tissues, we investigated the role these antagonists play in regulating lens cell proliferation and differentiation, and their contribution to lens structure and growth. Using established mice lines deficient for either or both Spred 1 and Spred 2, we demonstrate their role in regulating lens development by negatively regulating ERK1/2 activity. Mice deficient for both Spred 1 and Spred 2 have impaired lens and eye development, displaying irregular lens epithelial and fibre cell activity as a result of increased levels of phosphorylated ERK1/2. While Spred 1 and Spred 2 do not appear to be necessary for induction and early stages of lens morphogenesis (prior to E11.5), nor for the formation of the primary fibre cells, they are required for the continuous embryonic growth and differentiation of the lens.

中文翻译：

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负调节的Spred1和Spred2蛋白是晶状体和眼睛形态发生所必需的。

人工晶状体的透明性和屈光性取决于其精确的细胞结构，并通过调节生命中必不可少的晶状体细胞增殖和分化过程来支持。ERK / MAPK信号通路在调节晶状体细胞的增殖和分化中起着至关重要的作用，进而受到包括Spred家族蛋白在内的抑制性分子的调控，从而调节和减弱生长因子刺激的影响。鉴于Spreds在晶状体中强烈而独特地表达，以及它们在一系列不同组织中确立的抑制作用，我们研究了这些拮抗剂在调节晶状体细胞增殖和分化中所发挥的作用，以及它们对晶状体结构和生长的贡献。使用既有的Spred 1和Spred 2或二者均缺乏的小鼠品系，我们通过负调节ERK1 / 2活性来证明其在调节晶状体发育中的作用。缺乏Spred 1和Spred 2的小鼠的晶状体和眼睛发育受损，由于磷酸化ERK1 / 2的水平升高，显示不规则的晶状体上皮和纤维细胞活性。虽然Spred 1和Spred 2对于诱导晶状体形态发生和早期阶段（在E11.5之前）或初级纤维细胞的形成似乎不是必需的，但它们对于持续的胚胎生长和分化是必需的。镜片。由于磷酸化的ERK1 / 2水平升高，显示不规则的晶状体上皮和纤维细胞活性。虽然Spred 1和Spred 2似乎对于晶状体形态发生的诱导和早期阶段（在E11.5之前）或初级纤维细胞的形成不是必需的，但它们对于持续的胚胎生长和分化是必需的。镜片。由于磷酸化的ERK1 / 2水平升高，显示不规则的晶状体上皮和纤维细胞活性。虽然Spred 1和Spred 2对于诱导晶状体形态发生和早期阶段（在E11.5之前）或初级纤维细胞的形成似乎不是必需的，但它们对于持续的胚胎生长和分化是必需的。镜片。