Essential roles of Tbx3 in embryonic skin development during epidermal stratification

Stepwise differentiation of epidermal cells is essential for development of stratified epithelium, but the underlying mechanisms remain unclear. Here, we show that Tbx3, a member of the T‐box family of transcription factors, plays a pivotal role in this mechanism. Tbx3 is expressed in both basal and...

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Published in:Genes to cells : devoted to molecular & cellular mechanisms 2017-03, Vol.22 (3), p.284-292
Main Authors: Ichijo, Ryo, Iizuka, Yui, Kubo, Hirokazu, Toyoshima, Fumiko
Format: Article
Language:English
Subjects:
Animals
Cell division
Epidermis - cytology
Epidermis - embryology
Epidermis - metabolism
Gene Expression
Mice, Inbred C57BL
Mice, Knockout
Rodents
T-Box Domain Proteins - physiology
Transcription Factor HES-1 - genetics
Transcription Factor HES-1 - metabolism
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Summary:Stepwise differentiation of epidermal cells is essential for development of stratified epithelium, but the underlying mechanisms remain unclear. Here, we show that Tbx3, a member of the T‐box family of transcription factors, plays a pivotal role in this mechanism. Tbx3 is expressed in both basal and suprabasal cells in the interfollicular epidermis of mouse embryos. Epidermis‐specific Tbx3 conditional knockout (cKO) embryos are small in size and display a thinner epidermis with an impaired barrier function. In the Tbx3 cKO epidermis, keratin 5‐positive undifferentiated cells, which reside in both basal and suprabasal layers of wild‐type embryos, are localized exclusively in the basal layer. In addition, mRNA expression levels of granular cell markers are increased in the Tbx3 cKO epidermis, suggesting that Tbx3 prevents premature differentiation of spinous cells. We further show that Tbx3 maintains the proliferative potential of basal cells and ensures their planar‐oriented cell division. Moreover, Tbx3 is shown to be required for the expression of Hes1, a well‐known Notch signaling target protein that is essential for epidermal development. We therefore propose that Tbx3 functions upstream of Hes1 to regulate proliferation and differentiation of basal and suprabasal cells during epidermal development. Tbx3 is required for the epidermal development and skin barrier acquisition.
ISSN:1356-9597
1365-2443
DOI:10.1111/gtc.12476