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.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Dermatologi och venereologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Dermatology and Venereal Diseases hsv//eng
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

Weiner, Lorin (författare)
Sharova, Tatyana Y (författare)
Siebenhaar, Frank (författare)
Atoyan, Ruzanna (författare)
Reginato, Anthony M (författare)
McNamara, Coleen A (författare)
Funa, Keiko,1949Gothenburg University,Göteborgs universitet,Institutionen för anatomi och cellbiologi,Institute of Anatomy and Cell Biology(Swepub:gu)xfunke (författare)
Gilchrest, Barbara A (författare)
Brissette, Janice L (författare)
Botchkarev, Vladimir A (författare)
Göteborgs universitetInstitutionen för anatomi och cellbiologi (creator_code:org_t)

Av författaren/redakt...: Sharov, Andrei A; Weiner, Lorin; Sharova, Tatyana ...; Siebenhaar, Fran ...; Atoyan, Ruzanna; Reginato, Anthon ...; visa fler...; McNamara, Coleen ...; Funa, Keiko, 194 ...; Gilchrest, Barba ...; Brissette, Janic ...; Botchkarev, Vlad ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Dermatologi och ...

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