| First Author | Hislop NR | Year | 2008 |
| Journal | Dev Biol | Volume | 321 |
| Issue | 1 | Pages | 263-72 |
| PubMed ID | 18619436 | Mgi Jnum | J:138857 |
| Mgi Id | MGI:3806729 | Doi | 10.1016/j.ydbio.2008.06.026 |
| Citation | Hislop NR, et al. (2008) Grhl3 and Lmo4 play coordinate roles in epidermal migration. Dev Biol 321(1):263-72 |
| abstractText | 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 LIM-only domain protein, LMO4 serves as a functional partner of GRHL3 in its established roles, and define a new cooperative role for these factors in 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 in 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. |
