Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation.

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

Nyckelord

Adenoviridae

genetics

metabolism

Animals

Apoptosis

physiology

Biological Markers

Bone Morphogenetic Protein Receptors

Bone Morphogenetic Proteins

antagonists & inhibitors

metabolism

Carrier Proteins

Cell Differentiation

physiology

Culture Techniques

DNA-Binding Proteins

metabolism

Embryo

Mammalian

anatomy & histology

physiology

Epidermal Growth Factor

metabolism

Epidermis

cytology

growth & development

physiology

Eyelids

cytology

growth & development

Genetic Vectors

Growth Differentiation Factor 5

Humans

In Situ Hybridization

In Situ Nick-End Labeling

Keratin-5

Keratinocytes

cytology

physiology

Keratins

genetics

Mice

Mice

Transgenic

Morphogenesis

physiology

Neoplasm Proteins

metabolism

Promoter Regions

Genetic

Proteins

genetics

metabolism

Receptors

Growth Factor

genetics

metabolism

Signal Transduction

physiology

Smad Proteins

Trans-Activators

metabolism

Transforming Growth Factor alpha

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)