Phosphorylation And Sumoylation Of CREB In Mouse Lens Development

The eye is an important visual organ in human and animal.Structurally,it contains three major tissues including cornea,lens and retina.During phototransduction,light is reflected by cornea and focused by lens into retina in which both rods and cones receive the light signal and convert it into electric signal.The electric signal is transmitted through intermediate neurons(bipolar cells and amacrine cells)and converged to ganglion cells whose axons pass through the visual disc and link to the neurons in the brain where electric signals were processed into image.During eye development,the ectoderm contacted by the optic vesicle becomes thickened,invaginated and extended,forming the lens vesicle.Once the lens vesicle is formed,the epithelial cells in the posterior move forward towards the lumen and differentiate into primary lens fiber cells.At the same time,the epithelial cells in the anterior migrate towards subequatorial region called germinal zone where they divide,and one of the two divided cells move to the equatorial region,differentiating into secondary fiber cells.the remaining cell keep dividing and repeat the same cycle.The matured lens contains the anterior epithelial cells and the inside fiber cells.During lens development,a series of transcription factors sequentially regulate lens differentiation.The cAMP response element binding protein(CREB)is a major transcription factor that regulates brain functions.In our recent study,we have shown that CREB is activated through phosphorylation at S133 by oxidative stress.Through suppression of alphaB-crystallin,CREB mediates oxidative stress-induced apoptosis.Whether CREB can regulate lens differentiation remains to be further studied.In the present thesis,modern biotechnologies and methods were used to examine the expression and activation of CREB inthe developing mouse eye lens.It was found that CREB is highly expressed in the lens epithelial cells.CREB phosphorylation at S133,however,is only observed in the differentiating fiber cells in the equatorial region.These results clearly show that CREB is implicated in control of lens differentiation.Moreover,we conducted analysis of CREB sumoylation during lens development.It was discovered that CREB can be conjugated with SUMO1 at ED 13.5 and 14.5.Together,our results provide clear in vivo evidence that CREB is implicated in control of lens development.Moreover,CREB function can be modulated through SUMO1 conjugation during lens development.