EHF is essential for epidermal and colonic epithelial homeostasis, and suppresses Apc-initiated colonic tumorigenesis.

2021-06-15

Reehorst, Camilla M

Nightingale, Rebecca

Luk, Ian Y

Jenkins, Laura

Koentgen, Frank

Williams, David S

Darido, Charbel

Tan, Fiona

Anderton, Holly

Chopin, Michael

Schoffer, Kael

Eissmann, Moritz F

Buchert, Michael

Mouradov, Dmitri

Sieber, Oliver M

Ernst, Matthias

Dhillon, Amardeep S

Mariadason, John M

Adenoma

Colon

Differentiation

EHF

Epidermis

Epithelium

Ets

Journal Article

0000-0002-8039-3582

0000-0001-9123-7684

10.1242/dev.199542

Ets homologous factor (EHF) is a member of the epithelial-specific Ets (ESE) family of transcription factors. To investigate its role in development and epithelial homeostasis, we generated a series of novel mouse strains in which the Ets DNA-binding domain of Ehf was deleted in all tissues (Ehf-/-) or specifically in the gut epithelium. Ehf-/- mice were born at the expected Mendelian ratio, but showed reduced body weight gain, and developed a series of pathologies requiring most Ehf-/- mice to reach an ethical endpoint before reaching 1 year of age. These included papillomas in the facial skin, abscesses in the preputial glands (males) or vulvae (females), and corneal ulcers. Ehf-/-mice also displayed increased susceptibility to experimentally induced colitis, which was confirmed in intestinal-specific Ehf knockout mice. Gut-specific Ehf deletion also impaired goblet cell differentiation, induced extensive transcriptional reprogramming in the colonic epithelium and enhanced Apc-initiated adenoma development. The Ets DNA-binding domain of EHF is therefore essential for postnatal homeostasis of the epidermis and colonic epithelium, and its loss promotes colonic tumour development.

link

Development 2021; 148(12): dev199542

Development