title: Essential roles of Tbx3 in embryonic skin development during epidermal stratification.
abstract: 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.
authors.affiliation: Department of Biosystems Science, Institute for Frontier Life and Medical Science, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.|Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ichijo
authors.affiliation: Department of Biosystems Science, Institute for Frontier Life and Medical Science, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.|Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Iizuka
authors.affiliation: Department of Biosystems Science, Institute for Frontier Life and Medical Science, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.|Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kubo
authors.affiliation: Department of Biosystems Science, Institute for Frontier Life and Medical Science, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.|Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Toyoshima
mesh_terms: D000818:Animals; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism; D015870:Gene Expression; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020825:T-Box Domain Proteins / Q000502:physiology*; D000072056:Transcription Factor HES-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C489734:Hes1 protein, mouse; D020825:T-Box Domain Proteins; C106884:TBX3 protein, human; D000072056:Transcription Factor HES-1