Grhl3 and Lmo4 play coordinate roles in epidermal migration
Grhl3 and Lmo4 play coordinate roles in epidermal migration
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DOI：
10.1016/j.ydbio.2008.06.026
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发表时间：
2008-09-01
影响因子：
2.7
通讯作者：
Jane, Stephen M.
中科院分区：
文献类型：
--
作者：
Hislop, Nikki R.;Caddy, Jacinta;Jane, Stephen M.
In addition to its role in formation of the epidermal barrier, the mammalian transcription factor Grainy head-like 3 (Grhl3) is also essential for neural tube closure and Wound repair, processes that are dependent in part on epidermal migration. Here, we demonstrate that the LIMI-only domain protein, LMO4 serves as a functional partner of GRHL3 in its established roles, and define a new cooperative role for these factors ill another developmental epidermal migration event, eyelid fusion. GRHL3 and LMO4 interact biochemically and genetically, with mutant mice exhibiting fully penetrant exencephaly, thoraco-lumbo-sacral spina bifida, defective skin barrier formation, and a co-incident eyes-open-at-birth (EOB) phenotype, which is not observed in the original individual null lines. The two genes are co-expressed ill the surface ectoderm of the migrating eyelid root, and electron microscopy of Grhl3/Lmo4-null eyes reveals a failure in epithelial extension and a lack of peridermal clump formation at the eyelid margins. Accumulation of actin fibers is also absent in the circumference of these eyelids, and ERK1/2 phosphorylation is lost in the epidermis and eyelids of Grhl3(-/-)/Lmo4(-/-) embryos. Keratinocytes from mutant mice fail to "heal" in in vitro scratch assays, consistent with a general epidermal migratory defect that is dependent on ERK activation and actin cable formation. (C) 2008 Elsevier Inc. All rights reserved.
