First Author | Chalmers FE | Year | 2022 |
Journal | Dev Biol | Volume | 485 |
Pages | 9-23 | PubMed ID | 35227671 |
Mgi Jnum | J:324926 | Mgi Id | MGI:7282000 |
Doi | 10.1016/j.ydbio.2022.02.009 | Citation | Chalmers FE, et al. (2022) Targeted deletion of TGFbeta1 in basal keratinocytes causes profound defects in stratified squamous epithelia and aberrant melanocyte migration. Dev Biol 485:9-23 |
abstractText | Transforming Growth Factor Beta 1 (TGFbeta1) 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 TGFbeta1 and regulation of epithelial development. To address this, we deleted TGFbeta1 in basal keratinocytes of stratified squamous epithelia. Newborn mice with a homozygous TGFbeta1 deletion had significant defects in proliferation and differentiation of the epidermis and oral mucosa, and died shortly after birth. Hair follicles were sparse in TGFbeta1 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 TGFbeta1 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 TGFbeta1 null newborn epidermis but expanded in the postnatal acanthotic epidermis of TGFbeta1 hemizygous mice. Thus, TGFbeta1 is both essential and haploinsufficient with context dependent roles in stratified squamous epithelial development and homeostasis. |