Related Experiment Videos
Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation
Andrei A Sharov1, Lorin Weiner, Tatyana Y Sharova
1Department of Dermatology, Boston University School of Medicine, 609 Albany Street, Boston, MA 02118, USA.
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.
Insights
Bone morphogenetic protein (BMP) signaling is crucial for eyelid opening during eye development. Inhibiting BMP signaling, by overexpressing noggin, delays eyelid opening and skin remodeling in mice.
Area of Science:
- Developmental Biology
- Molecular Biology
- Ophthalmology
Background:
- Sensory organ development requires skin openings for environmental interaction.
- Eyelid development involves growth, fusion, and subsequent reopening to allow visual input.
Purpose of the Study:
- To investigate the role of bone morphogenetic protein (BMP) signaling in eyelid opening and eye morphogenesis.
- To elucidate the molecular mechanisms regulating eyelid opening.
Main Methods:
- Utilized transgenic mice overexpressing the BMP antagonist noggin under the keratin 5 (K5) promoter.
- Employed adenovirus vectors to enhance expression of a kinase-inactive BMP receptor (BMPR-IB) in wild-type mice.
- Performed ex vivo culture of eyelid explants to assess the effects of BMP-4, EGF, and TGF-alpha.
Main Results:
- Overexpression of noggin in the epidermis significantly inhibited eyelid opening in transgenic mice.
- Enhanced BMPR-IB expression also inhibited eyelid opening in wild-type mice.
- Noggin overexpression reduced apoptosis and delayed cell differentiation in the eyelid epithelium, downregulating apoptotic receptors and keratinocyte markers.
- BMP-4, but not EGF or TGF-alpha, accelerated eyelid opening in cultured explants from K5-Noggin mice.
Conclusions:
- The BMP signaling pathway is a key regulator of eyelid opening and skin remodeling during eye development.
- BMP signaling influences genetic programs controlling apoptosis and cell differentiation in the eyelid epithelium.
- These findings highlight BMPs as critical mediators in the final stages of eye morphogenesis.