Noggin Overexpression Inhibits Eyelid Opening by Altering Epidermal Apoptosis and Differentiation

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2003 Jun 14

PMID 12805214

Citations 35

Authors

Andrei A Sharov

Lorin Weiner

Tatyana Y Sharova

Frank Siebenhaar

Ruzanna Atoyan

Anthony M Reginato

Coleen A McNamara

Keiko Funa

Barbara A Gilchrest

Janice L Brissette

Vladimir A Botchkarev

Affiliations

Soon will be listed here.

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-alpha, 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.

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