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Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation
Author(s) -
Sharov Andrei A.,
Weiner Lorin,
Sharova Tatyana Y.,
Siebenhaar Frank,
Atoyan Ruzanna,
Reginato Anthony M.,
McNamara Coleen A.,
Funa Keiko,
Gilchrest Barbara A.,
Brissette Janice L.,
Botchkarev Vladimir A.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg291
Subject(s) - biology , noggin , apoptosis , microbiology and biotechnology , eyelid , cancer research , genetics , gene , bone morphogenetic protein , medicine , surgery
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‐α, 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.