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Ting SB, Caddy J, Wilanowski T, et al. The epidermis of grhl3-null mice displays altered lipid processing and cellular hyperproliferation. Organogenesis. 2005;2(2):33-5doi: 10.4161/org.2.2.2167.
Ting, S. B., Caddy, J., Wilanowski, T., Auden, A., Cunningham, J. M., Elias, P. M., Holleran, W. M., & Jane, S. M. (2005). The epidermis of grhl3-null mice displays altered lipid processing and cellular hyperproliferation. Organogenesis, 2(2), 33-5. https://doi.org/10.4161/org.2.2.2167
Ting, Stephen B, et al. "The epidermis of grhl3-null mice displays altered lipid processing and cellular hyperproliferation." Organogenesis vol. 2,2 (2005): 33-5. doi: https://doi.org/10.4161/org.2.2.2167
Ting SB, Caddy J, Wilanowski T, Auden A, Cunningham JM, Elias PM, Holleran WM, Jane SM. The epidermis of grhl3-null mice displays altered lipid processing and cellular hyperproliferation. Organogenesis. 2005 Apr;2(2):33-5. doi: 10.4161/org.2.2.2167. PMID: 19521564; PMCID: PMC2634083.
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Organogenesis. 2005 Apr;2(2):33-5. doi: 10.4161/org.2.2.2167.

The epidermis of grhl3-null mice displays altered lipid processing and cellular hyperproliferation.

Organogenesis

Stephen B Ting, Jacinta Caddy, Tomasz Wilanowski, Alana Auden, John M Cunningham, Peter M Elias, Walter M Holleran, Stephen M Jane

Affiliations

  1. Rotary Bone Marrow Research Laboratories; Parkville, Victoria Australia.

PMID: 19521564 PMCID: PMC2634083 DOI: 10.4161/org.2.2.2167

Abstract

The presence of an impermeable surface barrier is an essential homeostatic mechanism in almost all living organisms. We have recently described a novel gene that is critical for the developmental instruction and repair of the integument in mammals. This gene, Grainy head-like 3 (Grhl3) is a member of a large family of transcription factors that are homologs of the Drosophila developmental gene grainy head (grh). Mice lacking Grhl3 fail to form an adequate skin barrier, and die at birth due to dehydration. These animals are also unable to repair the epidermis, exhibiting failed wound healing in both fetal and adult stages of development. These defects are due, in part, to diminished expression of a Grhl3 target gene, Transglutaminase 1 (TGase 1), which encodes a key enzyme involved in cross-linking of epidermal structural proteins and lipids into the cornified envelope (CE). Remarkably, the Drosophila grh gene plays an analogous role, regulating enzymes involved in the generation of quinones, which are essential for cross-linking structural components of the fly epidermis. In an extension of our initial analyses, we focus this report on additional defects observed in the Grhl3-null epidermis, namely defective extra-cellular lipid processing, altered lamellar lipid architecture and cellular hyperproliferation. These abnormalities suggest that Grhl3 plays diverse mechanistic roles in maintaining homeostasis in the skin.

Keywords: Grhl3; grainy head; lipids; proliferation; skin barrier

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