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Jeff C. Tarr Professor of Molecular and Cellular Biology, Emeritus

Joshua Sanes

Jeff C. Tarr Professor of Molecular and Cellular Biology, Emeritus

Research

Key questions in neuroscience are: how are complex neural circuits assembled in young animals and how do they process information in adults?

The retina may be the first part of the mammalian brain for which satisfactory answers to these questions will be obtained. The retina is about as complex as any other part of the brain, but it has several features that facilitate analysis: it is accessible, compact, and structurally regular, and we already know a lot about what it does.

Visual information is passed from retinal photoreceptors to interneurons to retinal ganglion cells (RGCs) and then on to the rest of the brain. Each RGC responds to a visual feature –for example motion in a particular direction– based on which of the interneuronal types synapse on it. In one set of studies, we used single cell transcriptomic methods to generate an atlas of all retinal cell types in mice, identifying 46 types of RGCs and some 80 types of interneurons. We extended these studies to generate atlases of 20 vertebrate species, allowing us to trace the evolution of these cell types over hundreds of millions of years. To understand how these circuits form, we marked retinal cell types transgenically in mice, mapped their connections, sought recognition molecules that mediate their connectivity, used genetic methods to manipulate these molecules, and assessed the structural and functional consequences of removing or swapping them.

Selected Publications

Lefebvre, JL, Kostadinov, D, Chen WV, Maniatis, T and Sanes, JR. Protocadherins Mediate Dendritic Self-Avoidance In The Mammalian Nervous System. Nature 2012; 488:517-521. 

Duan X, Krishnaswamy A, De la Huerta I, and Sanes JR. Type II cadherins guide assembly of a direction-selective retinal circuit. Cell 2014; 158: 793-807.

Krishnaswamy A, Yamagata M, Duan X, Hong YK, and Sanes JR. Sidekick 2 directs formation of a retinal pathway that detects differential motion.  Nature 2015; 524:466-70.

Peng YR, Shekhar K, Yan W, Herrmann D, Sappington A, Bryman GS, van Zyl T, Do MTH, Regev A, Sanes JR. Molecular classification and comparative taxonomics of foveal and peripheral cells in primate retina. Cell 2019; 176:1222-1237

Jacobi A, Tran N, Yan W*, Benhar I, Tian F, Schaffer R, He Z, Sanes JR. Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells. Neuron 2022; 110:2625-2645.

Hahn J, Monavarfeshani A, Qiao M, Kao A, Kölsch Y, Kumar A, Kunze VP, Rasys AM, Richardson R, Baier H, Lucas RJ, Li W, Meister M, Trachtenberg JT, Yan W, Peng YR, Sanes JR, Shekhar K.  Evolution of neuronal cell classes and types in the vertebrate retina. Nature; 624:415-424