The epidermal growth factor receptor decreases S tathmin 1 and triggers catagen entry in the mouse

• Published in: Experimental dermatology Vol. 25; no. 4; pp. 275 - 281
• Main Authors: Bichsel, Kyle J., Hammiller, Brianna, Trempus, Carol S., Li, Yanhua, Hansen, Laura A.
• Format: Journal Article
• Language: English
• Published: 01-04-2016
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.12921

The epidermal growth factor receptor (
EGFR
) is necessary for normal involution of hair follicles after the growth phase of anagen, although the mechanisms through which it acts are not well understood. In this report, we used transcriptional profiling of microdissected hair follicles from mice with skin‐targeted deletion of
Egfr
to investigate how
EGFR
activation triggers catagen. Immunofluorescence for phospho‐
EGFR
in mouse skin revealed increased activation of
EGFR
in follicular keratinocytes at catagen onset. Consistent with other models of
EGFR
deficiency, mice with skin‐targeted deletion of
Egfr
(
Krt14‐Cre
+
/Egfr
fl/fl
) exhibited a delayed and asynchronous catagen entry. Transcriptional profiling at the time of normal catagen onset at post‐natal day (P) 17 revealed increased expression of the mitotic regulator
Rcc2
in hair follicles lacking
EGFR
. Rcc2 protein was strongly immunopositive in the nuclei of control follicular keratinocytes at P16 then rapidly decreased until it was undetectable between P18 and 21. In contrast, Rcc2 expression continued in
Egfr
mutant follicles throughout this period. Proliferation, measured by bromodeoxyuridine incorporation, was also significantly increased in
Egfr
mutant follicular keratinocytes compared to controls at P18‐21. Similarly, Rcc2‐regulated mitotic regulator Stathmin 1 was strikingly reduced in control but not
Egfr
mutant follicles between P17 and P19. Deletion of
Stmn1
, in turn, accelerated catagen entry associated with premature cessation of proliferation in the hair follicles. These data reveal
EGFR
suppression of mitotic regulators including Rcc2 and Stathmin 1 as a mechanism for catagen induction in mouse skin.