Noggin is a mesenchymally derived stimulator of hair-follicle induction

Abstract

The induction of developmental structures derived from the ectoderm, such as the neural tube or tooth, occurs through neutralization of the inhibitory activity of members of the bone-morphogenetic protein (BMP) family by BMP antagonists. Here we show that, during hair-follicle development, the neural inducer and BMP-neutralizing protein Noggin is expressed in the follicular mesenchyme, that noggin-knockout mice show significant retardation of hair-follicle induction, and that Noggin neutralizes the inhibitory action of BMP-4 and stimulates hair-follicle induction in embryonic skin organ culture. As a crucial mesenchymal signal that stimulates hair-follicle induction, Noggin operates through antagonistic interactions with BMP-4, which result in upregulation of the transcription factor Lef-1 and the cell-adhesion molecule NCAM, as well as through BMP4-independent downregulation of the 75 kD neurotrophin receptor in the developing hair follicle.

Bmp signaling is required for intestinal growth and morphogenesis

“…Again, the mechanisms underlying this suppression are not clear. One possibility is that Bmp and Wnt signaling have an antagonistic function in the intestine similar to that seen in hair follicle induction in the skin, where Wnt signaling promotes and Bmp signaling inhibits hair follicle formation (Gat et al, 1998;Botchkarev et al, 1999).…”

Bone Morphogenetic Protein Antagonist Noggin Promotes Skin Tumorigenesis via Stimulation of the Wnt and Shh Signaling Pathways

“…6 Many indications suggest BMP signaling as a powerful regulator of cell proliferation and differentiation in developing and postnatal skin. BMP signaling inhibits the initiation phase of hair follicle (HF) development 9 and is required for proper control of keratinocyte differentiation into HF-specific cell lineages. 10 -13 In adult skin, BMP signaling is involved in the control of HF cycling, HF size, and in hair pigmentation.…”

Proliferation and cornification during development of the mammalian epidermis

“…High levels of BMP-6 transcript and protein are present in the suprabasal layers of the epidermis of mouse embryos starting from E15.5, while BMP-7 mRNA is seen in the basal layer during the later stages of embryonic development (Wall et al, 1993;Takahashi and Ikeda, 1996). BMPR-IA is expressed in the basal layer of murine epidermis at E16.5, while BMPR-IB expression is restricted to the suprabasal keratinocytes (Botchkarev et al, 1999). Smad1, 5, 6, and 7 are also abundantly expressed in the developing epidermis (Dick et al, 1998;Flanders et al, 2001;He et al, 2001).…”

“…High expression inhibits epidermal proliferation, while lower levels of expression stimulate proliferation and lead to the appearance of proliferating K14-positive cells in the suprabasal layer (Blessing et al, 1996). Excessive BMP activity in Noggin-deficient mice (Noggin functions as an antagonist of BMP signaling) (Zimmerman et al, 1996) also results in increased epidermal proliferation, downregulation of K10, and ectopic proliferating cells that express K14 in the suprabasal layers (Botchkarev et al, 1999(Botchkarev et al, , 2002.…”