Lens-specific expression of PDGF-A alters lens growth and development.
The vertebrate lens provides an in vivo model to study the molecular mechanisms by which growth factors influence development decisions. In this study, we have investigated the expression patterns of platelet-derived growth factor (PDGF) and PDGF receptors during murine eye development by in situ hybridization. Postnatally, PDGF-A is highly expressed in the iris and ciliary body, the ocular tissues closest to the germinative zone of the lens, a region where most proliferation of lens epithelial cells occurs. PDGF-A is also present in the corneal endothelium anterior to the lens epithelium in embryonic and early postnatal eyes. PDGF-B is expressed in the iris and ciliary body as well as in the vascular cells which surround the lens during early eye development. In the lens, expression of PDGF-alpha receptor (PDGF-alphaR), a receptor that can bind both PDGF-A and PDGF-B, is restricted to the lens epithelium throughout life. The expression of PDGF-alphaR in the lens epithelial cells and PDGF (A- and B-chains) in the ocular tissues adjacent to the lens suggests that PDGF signaling may play a key role in regulating lens development. To further examine how PDGF affects lens development in vivo, we generated transgenic mice that express human PDGF-A in the lens under the control of the alphaA-crystallin promoter. The transgenic mice exhibit lenticular defects that result in cataracts. The percentage of surface epithelial cells in S-phase is increased in transgenic lenses compared to their nontransgenic littermates. Higher than normal levels of cyclin A and cyclin D2 expression were also detected in transgenic lens epithelium. These results together suggest that PDGF-A can induce a proliferative response in lens epithelial cells. The lens epithelial cells in the transgenic mice also exhibit characteristics of differentiating fiber cells. For example, the transgenic lens epithelial cells are slightly elongated, contain larger and less condensed nuclei, and express fiber-cell-specific beta-crystallins. Our results suggest that PDGF-A normally acts as a proliferative factor for the lens epithelial cells in vivo. Elevated levels of PDGF-A enhance proliferation, but also appear to induce some aspects of the fiber cell differentiation pathway.
Reneker
L W
LW
Department of Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA. lreneker@condor.bcm.tmc.edu
Overbeek
P A
PA
D000375:Aging; D000818:Animals; D002454:Cell Differentiation; D003459:Crystallins / Q000096:biosynthesis / Q000235:genetics; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis; D005314:Embryonic and Fetal Development; D004847:Epithelial Cells; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D007908:Lens, Crystalline / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis*; D014158:Transcription, Genetic
C080336:CCND2 protein, human; C486196:Ccnd2 protein, mouse; D003459:Crystallins; D056742:Cyclin D2; D016213:Cyclins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor