|About GSBS | FAQ | Job Opportunities | Search UMDNJ|
B.S. Nanjing University – 2005
Thesis Advisor: Richard S. Nowakowski, Ph.D.
Graduate Program in Cell & Developmental Biolog
Research Tower, Room V-10
Monday, October 4, 2010
In the retina of adult albino mammals multiple abnormalities have been reported, including a deficit of rods and a decrease in ipsilaterally-projecting axons. A variety of genetic disruptions of retinal pigmentation can produce these abnormalities, suggesting that there is some common final pathway. We propose that the perturbation of cell proliferation and neuron production during the earliest stages of retina development accounts for the altered composition of different cell types in albino adults. To demonstrate and quantify this perturbation, we employed double S-phase labeling in 2 inbred mouse strains: C57BL/6J (pigmented) and C57BL/6J-c2J (albino). Three independent labeling strategies employing both Bromodeoxyuridine (BrdU) and Iododeoxyuridine (IdU) to determine: 1) cell cycle parameters of the proliferating population on embryonic day 15 (E15), 2) the proportion of cells that exit cell cycle (Q cells) on E11 and E12, 3) the proportion of the Q cells that assume a ganglion cell fate on E11 and E12. All statistical comparisons were made in 50 ìm sectors along the ventricular surface from horizontal sections in the plane of the optic nerve to provide high spatio-temporal resolution. Both global and regional analyses show that cell cycle exit (Q) is affected in albino retina, with a delay on E11 and a catch-up on E12. In contrast the proportion of Q cells that become ganglion cells is unchanged, i.e., the neuron differentiation decision of postproliferative cells remain unaffected at these early ages. Combined with an in silico model of retinal neurogenesis developed from the Nowakowski Lab, the experimental studies for this work partially confirms the hypothesis that albinism affects retinal neurogenesis by perturbing cell cycle exit but not neuron differentiation.