TGFbeta2 in corneal morphogenesis during mouse embryonic development.
To examine the roles of TGFbeta isoforms on corneal morphogenesis, the eyes of mice that lack TGFbetas were analyzed at different developmental stages for cell proliferation, migration and apoptosis, and for expression patterns of keratin 12, lumican, keratocan and collagen I. Among the three Tgfb(-/-) mice, only Tgfb2(-/-) mice have abnormal ocular morphogenesis characterized by thin corneal stroma, absence of corneal endothelium, fusion of cornea to lens (a Peters'-like anomaly phenotype), and accumulation of hyaline cells in vitreous. In Tgfb2(-/-) mice, fewer keratocytes were found in stroma that has a decreased accumulation of ECM; for example, lumican, keratocan and collagen I were greatly diminished. The absence of TGFbeta2 did not compromise cell proliferation, nor enhance apoptosis. The thinner stroma resulting from decreased ECM synthesis may account for the decreased cell number in the stroma of Tgfb2 null mice. Keratin 12 expression was not altered in Tgfb2(-/-) mice, implicating normal corneal type epithelial differentiation. Delayed appearance of macrophages in ocular tissues was observed in Tgfb2(-/-) mice. Malfunctioning macrophages may account for accumulation of cell mass in vitreous of Tgfb2 null mice.
Saika
S
S
Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, USA.
Saika
S
S
Liu
C Y
CY
Azhar
M
M
Sanford
L P
LP
Doetschman
T
T
Gendron
R L
RL
Kao
C W
CW
Kao
W W
WW
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D002455:Cell Division; D002465:Cell Movement; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D003315:Cornea / Q000166:cytology / Q000196:embryology*; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007632:Keratan Sulfate / Q000235:genetics / Q000378:metabolism; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D000071234:Lumican; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
D015820:Cadherins; D011508:Chondroitin Sulfate Proteoglycans; D024042:Collagen Type I; D024141:Collagen Type IV; C099280:Kera protein, mouse; C000604307:Lum protein, mouse; D000071234:Lumican; D020033:Protein Isoforms; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007633:Keratins; D007632:Keratan Sulfate; D000123:Acetyltransferases