Article ; Online: Targeted deletion of TGFβ1 in basal keratinocytes causes profound defects in stratified squamous epithelia and aberrant melanocyte migration.
2022 Volume 485, Page(s) 9–23
Abstract: Transforming Growth Factor Beta 1 (TGFβ1) is a multifunctional cytokine that regulates proliferation, apoptosis, and epithelial-mesenchymal transition of epithelial cells. While its role in cancer is well studied, less is known about TGFβ1 and regulation ...
| Abstract | Transforming Growth Factor Beta 1 (TGFβ1) is a multifunctional cytokine that regulates proliferation, apoptosis, and epithelial-mesenchymal transition of epithelial cells. While its role in cancer is well studied, less is known about TGFβ1 and regulation of epithelial development. To address this, we deleted TGFβ1 in basal keratinocytes of stratified squamous epithelia. Newborn mice with a homozygous TGFβ1 deletion had significant defects in proliferation and differentiation of the epidermis and oral mucosa, and died shortly after birth. Hair follicles were sparse in TGFβ1 depleted skin and had delayed development. Additionally, the Wnt pathway transcription factor LEF1 was reduced in hair follicle bulbs and nearly absent from the basal epithelial layer. Hemizygous knockout mice survived to adulthood but were runted and had sparse coats. The skin of these mice had irregular hair follicle morphology and aberrant hair cycle progression, as well as abnormally high melanin expression and delayed melanocyte migration. In contrast to newborn TGFβ1 null mice, the epidermis was hyperproliferative, acanthotic and inflamed. Expression of p63, a master regulator of stratified epithelial identity, proliferation and differentiation, was reduced in TGFβ1 null newborn epidermis but expanded in the postnatal acanthotic epidermis of TGFβ1 hemizygous mice. Thus, TGFβ1 is both essential and haploinsufficient with context dependent roles in stratified squamous epithelial development and homeostasis. |
|---|---|
| MeSH term(s) | Animals ; Carcinoma, Squamous Cell/metabolism ; Cell Differentiation ; Epidermis/metabolism ; Epithelium/metabolism ; Hair Follicle ; Keratinocytes ; Melanocytes ; Mice |
| Language | English |
| Publishing date | 2022-02-25 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. |
| ZDB-ID | 1114-9 |
| ISSN | 1095-564X ; 0012-1606 |
| ISSN (online) | 1095-564X |
| ISSN | 0012-1606 |
| DOI | 10.1016/j.ydbio.2022.02.009 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.B 508: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.