FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands
FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands
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DOI：
10.1242/dev.108944
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发表时间：
2014-07-01
期刊：
影响因子：
4.6
通讯作者：
Beebe, David C.
中科院分区：
文献类型：
--
作者：
Chen, Ziyan;Huang, Jie;Beebe, David C.
小鼠泪腺、哈氏腺和睑板腺从预期的结膜和眼睑上皮细胞发育而来，并产生润滑和保护眼表面的分泌物。早在E11.5，Sox 9表达定位于假定的结膜上皮，并且在泪腺和哈氏腺形成时在泪腺和哈氏腺中检测到。条件性缺失表明，Sox 9是泪腺和哈氏腺发育所必需的，并有助于睑板腺的形成。Sox 9调节Sox 10的表达，以促进泪腺中分泌腺泡叶的形成。Sox 9和FGF信号是泪腺发育早期软骨相关细胞外基质成分表达所必需的。眼表上皮中Fgfr 2缺失减少Sox 9并消除Sox 10表达。外胚层中Sox 9的缺失并不影响邻近间充质中Fgf 10的表达或上皮中Fgfr 2的表达，但似乎减少了FGF信号传导。Sox 9杂合子表现为单倍不足型，大多数情况下泪腺眶外分支缺失。然而，增强上皮FGF信号的组成型活性FGF受体的表达，只有部分拯救泪腺缺陷的Sox 9杂合子，这表明Sox 9，下游的FGF信号，在调节泪腺分支和分化的关键作用。
Murine lacrimal, harderian and meibomian glands develop from the prospective conjunctival and eyelid epithelia and produce secretions that lubricate and protect the ocular surface. Sox9 expression localizes to the presumptive conjunctival epithelium as early as E11.5 and is detected in the lacrimal and harderian glands as they form. Conditional deletion showed that Sox9 is required for the development of the lacrimal and harderian glands and contributes to the formation of the meibomian glands. Sox9 regulates the expression of Sox10 to promote the formation of secretory acinar lobes in the lacrimal gland. Sox9 and FGF signaling were required for the expression of cartilage-associated extracellular matrix components during early stage lacrimal gland development. Fgfr2 deletion in the ocular surface epithelium reduced Sox9 and eliminated Sox10 expression. Sox9 deletion from the ectoderm did not affect Fgf10 expression in the adjacent mesenchyme or Fgfr2 expression in the epithelium, but appeared to reduce FGF signaling. Sox9 heterozygotes showed a haploinsufficient phenotype, in which the exorbital branch of the lacrimal gland was absent in most cases. However, enhancement of epithelial FGF signaling by expression of a constitutively active FGF receptor only partially rescued the lacrimal gland defects in Sox9 heterozygotes, suggesting a crucial role of Sox9, downstream of FGF signaling, in regulating lacrimal gland branching and differentiation.