Open AccessCytoplasmic localization of GRHL3 upon epidermal differentiation triggers cell shape change for epithelial morphogenesis
Author(s) -
Chiharu Kimura-Yoshida,
Kyoko Mochida,
Muneo Nakaya,
Takeomi Mizutani,
Isao Matsuo
Publication year - 2018
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/s41467-018-06171-8
Subject(s) - morphogenesis , microbiology and biotechnology , wnt signaling pathway , transcription factor , cytoplasm , biology , cellular differentiation , cell polarity , embryoid body , epidermal growth factor , cell , chemistry , signal transduction , cell culture , genetics , adult stem cell , gene
Epithelial cell shape change is a pivotal driving force for morphogenesis of complex three-dimensional architecture. However, molecular mechanisms triggering shape changes of epithelial cells in the course of growth and differentiation have not been entirely elucidated. Grhl3 plays a crucial role as a downstream transcription factor of Wnt/ β-catenin in epidermal differentiation. Here, we show Grhl3 induced large, mature epidermal cells, enriched with actomyosin networks, from embryoid bodies in vitro. Such epidermal cells were apparently formed by the simultaneous activation of canonical and non-canonical Wnt signaling pathways. A nuclear transcription factor, GRHL3 is localized in the cytoplasm and cell membrane during epidermal differentiation. Subsequently, such extranuclear GRHL3 is essential for the membrane-associated expression of VANGL2 and CELSR1. Cytoplasmic GRHL3, thereby, allows epidermal cells to acquire mechanical properties for changes in epithelial cell shape. Thus, we propose that cytoplasmic localization of GRHL3 upon epidermal differentiation directly triggers epithelial morphogenesis.