Mechanisms of Retinal Ganglion Cell Patterning

University Of Washington, Seattle WA

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Abstract

DESCRIPTION (provided by applicant): The interplay of extrinsic and intrinsic signals in a cell determines its developmental fate. The retina is an excellent system for exploring both molecular and cellular interactions during development. Much is known about the type, timing and ultimate pattern of cells generated during retinogenesis, and certain molecular pathways involved in these processes are being elucidated. The cells of the retina are particularly suited to an analysis of the mechanisms by which patterned arrays of neurons arise during development, since the retinal neurons are organized in regular mosaics. The aim of this proposal is to investigate the molecular and cellular mechanisms that control retinal ganglion cell (RGC) differentiation and mosaic pattern formation. Specifically lateral inhibtion mediated by Notch-Delta signaling has been shown to influence RGC development, yet its precise role remains unclear as RGCs arise seperated by more than one cell diameter. I propose to investigate how Notch activity regulates RGC patterning, potentially mediated by a new soluble Notch ligand. The better understanding of the molecular and celluar basis of RGC formation may lead to the development of clinical treatments for retinal diseases such as glaucoma and macular degeneration.