A novel allele of Alx4 results in reduced Fgf10 expression and failure of eyelid fusion in mice.
A novel allele of Alx4 results in reduced Fgf10 expression and failure of eyelid fusion in mice.
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ALX4的新等位基因导致小鼠的FGF10表达和眼睑融合的失败。
DOI：
10.1007/s00335-015-9557-z
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发表时间：
2015-04
期刊：
影响因子：
2.5
通讯作者：
Murray, Stephen A.
中科院分区：
文献类型：
--
作者：
Curtain, Michelle;Heffner, Caleb S.;Maddox, Dennis M.;Gudis, Polyxeni;Donahue, Leah Rae;Murray, Stephen A.
发育中的眼睑的正常融合需要来自眼睑间充质的感应信号与周皮细胞层的迁移和眼睑在眼睛上的收缩的协调。这一过程的失败会导致小鼠出现出生时眼睑张开（EOB）的表型。我们已经鉴定出 Alx4 的一种新的自发等位基因，除了多指畸形和颅骨畸形之外，还表现出 EOB。Alx4 在眼睑融合之前和期间在眼睑间充质中表达，其区域与在正常眼睑发育中也发挥作用的基因的表达重叠。我们发现 Alx4 突变小鼠的 Fgf10 表达减少，Fgf10 是间充质中表达的关键因子，是周皮启动眼睑融合所需的。这伴随着表达磷酸化 c-Jun 的周皮细胞数量减少，与 Fgf10 表达的不完全消除一致。总之，这些数据表明小鼠眼睑融合需要 Alx4 的表达，同时伴随着眼睑融合途径重要成分正常表达的丧失。
Normal fusion of developing eyelids requires coordination of inductive signals from the eyelid mesenchyme with migration of the periderm cell layer and constriction of the eyelids across the eye. Failure of this process results in an eyelids open at birth (EOB) phenotype in mice. We have identified a novel spontaneous allele of Alx4 that displays EOB, in addition to polydactyly and cranial malformations.Alx4 is expressed in the eyelid mesenchyme prior to and during eyelid fusion in a domain overlapping the expression of genes that also play a role in normal eyelid development. We show that Alx4 mutant mice have reduced expression of Fgf10, a key factor expressed in the mesenchyme that is required for initiation of eyelid fusion by the periderm. This is accompanied by a reduced number of periderm cells expressing phosphorylated c-Jun, consistent with the incomplete ablation of Fgf10 expression. Together, these data demonstrate that eyelid fusion in mice requires the expression of Alx4, accompanied by the loss of normal expression of essential components of the eyelid fusion pathway.
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影响因子：
11.4
作者：
Zhang, L;Wang, W;Xia, Y
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