Grainyhead-like factor Get1/Grhl3 regulates formation of the epidermal leading edge during eyelid closure
Autor: | Jaana Männik, Zhengquan Yu, Bogi Andersen, Thu Pham, Xiaoman Xu, Ambica Bhandari |
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Jazyk: | angličtina |
Předmět: |
MAPK/ERK pathway
Keratinocytes TGF alpha Leading edge Grhl3/Get1 Grainyhead Biology Article 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Keratinocyte migration Transcription factor Molecular Biology 030304 developmental biology Mice Knockout 0303 health sciences integumentary system Neural tube Eyelids Ear Anatomy Cell Biology Transforming Growth Factor alpha Actins Cell biology Up-Regulation DNA-Binding Proteins medicine.anatomical_structure Eyelid sense organs Eyelid closure Signal transduction Epidermis 030217 neurology & neurosurgery Signal Transduction Transcription Factors Developmental Biology |
Zdroj: | Developmental Biology. (1):56-67 |
ISSN: | 0012-1606 |
DOI: | 10.1016/j.ydbio.2008.04.001 |
Popis: | Grainyhead transcription factors play an evolutionarily conserved role in regulating epidermal terminal differentiation. One such factor, the mammalian Grainyhead-like epithelial transactivator (Get1/Grhl3), is important for epidermal barrier formation. In addition to a role in barrier formation, Grainyhead genes play roles in closure of several structures such as the mouse neural tube and Drosophila wounds. Consistent with these observations, we found that Get1 knockout mice have an eye-open at birth phenotype. The failure of eyelid closure appears to be due to critical functions of Get1 in promoting F-actin polymerization, filopodia formation, and the cell shape changes that are required for migration of the keratinocytes at the leading edge during eyelid closure. The expression of TGFalpha, a known regulator of leading edge formation, is decreased in the eyelid tip of Get1(-/-) mice. Levels of phospho-EGFR and phospho-ERK are also decreased at the leading edge tip. Furthermore, in an organ culture model, TGFalpha can increase levels of phospho-EGFR and promote cell shape changes as well as leading edge formation in Get1(-/-) eyelids, indicating that in eyelid closure Get1 acts upstream of TGFalpha in the EGFR/ERK pathway. |
Databáze: | OpenAIRE |
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