Molecular determinants of the retinogeniculate projection

Abstract

The appropriate connections of retinal ganglion cells (RGC) to their thalamic target, the lateral geniculate nucleus (LGN), are essential for visual function and involve precise topographic mapping and arbor reorganization. My project will link molecular specification of both retina and LGN to the innervation of retinal fibers, still poorly understood in the mouse. The transcription factor Zic2, the guidance receptor EphB1, and the adhesion molecule NrCAM have been shown by Dr. Mason’s lab to specify the RGC axon growth in the optic chiasm. After delineating the spatiotemporal aspects of RGC innervation, I will assess the role of these molecules one step further in the pathway, in the targeting and patterning of retinal afferents in different topographic and eye-specific subdivisions of the LGN. My preliminary data implicates EphB1 in the topographic mapping of RGC fibers. Furthermore, EphB1 and Zic2 are expressed differentially in subregions of the LGN and might therefore also participate in target specification. My previous training in developmental neuroanatomy will be applied to a more defined and malleable system. I will learn additional approaches in Dr Mason’s lab as I determine a role for these genes by perturbing gene expression in transgenic models and by blocking or ectopically expressing genes in the system in vitro and in vivo. This work is essential to our understanding of the interplay between activity-dependent and molecular directives for retinogeniculate development. I will also benefit from the rich environment of Columbia University and aim to initiate collaborations important for my future career as researcher in France.