Grhl3 and Lmo4 play coordinate roles in epidermal migration

Hislop, NR; Caddy, J; Ting, SB; Auden, A; Vasudevan, S; King, SL; Lindeman, GJ; Visvader, JE; Cunningham, JM; Jane, SM

Author(s): Hislop, NR; Caddy, J; Ting, SB; Auden, A; Vasudevan, S; King, SL; Lindeman, GJ; Visvader, JE; Cunningham, JM; Jane, SM;
Details: Publication Year 2008-09-01,Volume 321,Issue #1,Page 263-272
Journal Title: DEVELOPMENTAL BIOLOGY
Publication Type: Journal Article
Abstract: 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.
Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords: DEVELOPMENTAL TRANSCRIPTION FACTORS; NEURAL-TUBE CLOSURE; MICE LACKING; EYELID DEVELOPMENT; GRAINY-HEAD; LIM DOMAIN; PLANAR POLARITY; LEADING-EDGE; EGF RECEPTOR; C-JUN
Publisher's Version: https://doi.org/10.1016/j.ydbio.2008.06.026
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2008-09-01 12:00:00