Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation.
Sharov, A.A. Weiner, L. Sharova, T.Y. Siebenhaar, F. Atoyan, R. Reginato, A.M. McNamara, C.A. Funa, K. Gilchrest, B.A. Brissette, J.L.
Sharov, A.A.
Weiner, L.
Sharova, T.Y.
Siebenhaar, F.
Atoyan, R.
Reginato, A.M.
McNamara, C.A.
Funa, K.
Gilchrest, B.A.
Brissette, J.L.
Publication Date
2003
End of Embargo
Supervisor
Keywords
Rights
Peer-Reviewed
Yes
Open Access status
closedAccess
Accepted for publication
Institution
Department
Awarded
Embargo end date
Collections
Additional title
Abstract
Contact of developing sensory organs with the external environment is established via the formation of openings in the skin. During eye development, eyelids first grow, fuse and finally reopen, thus providing access for visual information to the retina. Here, we show that eyelid opening is strongly inhibited in transgenic mice overexpressing the bone morphogenetic protein (BMP) antagonist noggin from the keratin 5 (K5) promoter in the epidermis. In wild-type mice, enhanced expression of the kinase-inactive form of BMPR-IB mediated by an adenovirus vector also inhibits eyelid opening. Noggin overexpression leads to reduction of apoptosis and retardation of cell differentiation in the eyelid epithelium, which is associated with downregulation of expression of the apoptotic receptors (Fas, p55 kDa TNFR), Id3 protein and keratinocyte differentiation markers (loricrin, involucrin). BMP-4, but not EGF or TGF-, accelerates opening of the eyelid explants isolated from K5-Noggin transgenic mice when cultured ex vivo. These data suggest that the BMP signaling pathway plays an important role in regulation of genetic programs of eyelid opening and skin remodeling during the final steps of eye morphogenesis.
Version
No full-text in the repository
Citation
Sharov AA, Weiner L, Sharova TY, et al (2003) Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation. The EMBO Journal. 22 (12): 2992-3003.
Link to publisher’s version
Link to published version
Link to Version of Record
Type
Article