title: Epithelial sheet movement requires the cooperation of c-Jun and MAP3K1.
abstract: Epithelial sheet movement is an essential morphogenetic process during mouse embryonic eyelid closure in which Mitogen-Activated Protein 3 Kinase 1 (MAP3K1) and c-Jun play a critical role. Here we show that MAP3K1 associates with the cytoskeleton, activates Jun N-terminal kinase (JNK) and actin polymerization, and promotes the eyelid inferior epithelial cell elongation and epithelium protrusion. Following epithelium protrusion, c-Jun begins to express and acts to promote ERK phosphorylation and migration of the protruding epithelial cells. Homozygous deletion of either gene causes defective eyelid closure, but non-allelic non-complementation does not occur between Map3k1 and c-Jun and the double heterozygotes have normal eyelid closure. Results from this study suggest that MAP3K1 and c-Jun signal through distinct temporal-spatial pathways and that productive epithelium movement for eyelid closure requires the consecutive action of MAP3K1-dependent cytoskeleton reorganization followed by c-Jun-mediated migration.
authors.affiliation: Department of Environmental Health, University of Cincinnati, College of Medicine.
authors.forename: Qinghang
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Environmental Health, University of Cincinnati, College of Medicine.
authors.forename: Maureen
authors.initials: M
authors.lastname: Mongan
authors.affiliation: Department of Environmental Health, University of Cincinnati, College of Medicine.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Environmental Health, University of Cincinnati, College of Medicine.
authors.forename: Jinling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, University of Cincinnati, College of Medicine.
authors.forename: Winston
authors.initials: W
authors.lastname: Kao
authors.affiliation: Department of Environmental Health, University of Cincinnati, College of Medicine.|Department of Ophthalmology, University of Cincinnati, College of Medicine.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D003599:Cytoskeleton / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000196:embryology*; D005143:Eyelids / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482578:Map3k1 protein, mouse
keywords: Embryonic eyelid closure; MAP3K1; c-Jun