Novel role for Grainy head in the regulation of cytoskeletal and junctional dynamics during epithelial repair

Abstract

Tissue repair is critical for the maintenance of epithelial integrity and permeability. Simple epithelial repair relies on a combination of collective cell movements and the action of a contractile actomyosin cable at the wound edge that together promote the fast and efficient closure of tissue discontinuities. The Grainy head family of transcription factors (Grh in flies; GRHL1-GRHL3 in mammals) are essential proteins that have been implicated both in the development and repair of epithelia. However, the genes and the molecular mechanisms that it controls remain poorly understood. Here, we show that Grh knockdown disrupts actomyosin dynamics upon injury of the pupa epithelial tissue. This leads to the formation of an ectopic actomyosin cable away from the wound edge and impaired wound closure. We also uncovered that E-Cadherin is downregulated in the Grh-depleted tissue around the wound, likely as a consequence of Dorsal (an NF-κB protein) misregulation, which also affects actomyosin cable formation. Our work highlights the importance of Grh as a stress response factor and its central role in the maintenance of epithelial characteristics necessary for tissue repair through regulating cytoskeleton and E-Cadherin dynamics.

Grhl3 promotes retention of epidermal cells under endocytic stress to maintain epidermal architecture in zebrafish

“…Transcription factors belonging to the highly conserved Grainyhead family act as important regulators of epidermal morphogenesis, wound healing, and barrier function [10][11][12][13][14][15][16]. Consistent with this, the three mammalian Grainyhead-like (Grhl) paralogs control the expression of genes important for cell adhesion and extracellular barrier repair.…”

Expression And Clinical Significance of Transcription Factor GRHL1 In Acute Myeloid Leukemia

“…[29] As a member of the GRHL family, GRHL1 plays an important role in regulating embryogenesis, embryonic development, formation of the epidermal barrier and repair of epidermal injury. [30][31][32][33] Furthermore, a great number of research have shown that the GRHL1 acted as a tumor suppressive factor in carcinogenesis, progression and prognosis of various cancer types including liver cancer, skin cancer, neuroblastoma and clear cell renal cell carcinoma. [34] GRHL1 plays a critical role in fate determination of pluripotent cells, which might be relevant to phenotypic plasticity in tumors.…”