Mechanisms of Lens Determination and Differentiation

Jin, Hong, Department of Biology, University of Virginia
Grainger, Robert, Department of Biology, University of Virginia
Adler, Paul, Department of Biology, University of Virginia
Green, Carla
Cronmiller, Claire, Department of Biology, University of Virginia
Desimone, Douglas, Department of Cell Biology, University of Virginia

Lens induction has been studied as a paradigm for studying tissue to tissue interactions for over a century. Although it has been established that lens formation is a step-wise process and that many molecules are involved, there are still many mysteries remaining regarding the mechanisms underlying lens formation. Focusing on the early embryonic events leading to lens formation, here I studied the commitment of tissue to a lens fate and the onset of subsequent lens differentiation. Commitment is a central aspect of organogenesis in all multicellular organisms. Acquisition of commitment is accomplished through an early phase of specification and a late phase of determination. Using widely accepted definitions of specification and determination, I studied commitment to lens formation in Xenopus. I am the first to distinguish a determination phase from a specification phase in the lens commitment process. Using an in vitro culture assay, I demonstrated that the transition from specification to determination is a tissue autonomous process. The difference between determination and specification was studied in both explant and transplant scenarios. Based on these different approaches, several gene products were proposed as candidate factors related to lens determination. Further studies on the roles of these candidate genes will help identify factors upstream of these candidate genes that are responsible for the lens determination process. Timing of any biological event is of great importance because disturbance in timing can cause severe developmental consequences. Here, by using -crystallin transgenic embryos that express GFP as an indicator of the onset of lens differentiation, I studied the embryonic factors regulating the onset of lens differentiation. I found that neural and mesendodermal tissues underlying the presumptive lens ectoderm can greatly promote iii the onset of lens differentiation. This promoting activity only exists in the anterior and dorsal regions of an embryo but not in the ventral and posterior regions, suggesting several candidate gene products that may control the onset of differentiation. In summary this study sheds light into the mechanisms of lens determination and provides insights into the embryological mechanism controlling the onset of lens differentiation. This work provides a strong basis for future work to identify gene products controlling these processes.

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PHD (Doctor of Philosophy)
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