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Jeff C. Tarr Professor of Molecular and Cellular Biology

Joshua Sanes

Jeff C. Tarr Professor of Molecular and Cellular Biology

Paul J. Finnegan Family Director, Center for Brain Science, Harvard University

(not taking students in 2018-2019)

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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 of ~25 types of RGC responds to a visual feature –for example motion in a particular direction– based on which of the ~70 interneuronal types synapse on it. To understand how these circuits form, we mark retinal cell types transgenically, map their connections, seek recognition molecules that mediate their connectivity, use genetic methods to manipulate these molecules, and assess the structural and functional consequences of removing or swapping them.

As a next step, we will ask how the RGCs transfer their information to their main target, the superior colliculus. We believe that our methods and results will be useful in tackling less accessible parts of the brain such as the cerebral cortex.

Selected Publications

Kay, JN, Chu, MW, Sanes, JR. Megf10 and 11 mediate homotypic interactions required for Mosaic spacing of retinal neurons.  Nature 2012; 483:465-469. 

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.

Duan X, Qiao, M, Bei F, Kim I-J, He Z and Sanes JR. Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling. Neuron 2015; 85:1244-56.

Shekhar K, Lapan SW, Whitney IE, Tran NM, Macosko EZ, Kowalczyk K, Adiconis X, Levin JZ, Nemesh J, Goldman M, McCarroll SA, Cepko CL, Regev A, and Sanes JR.  Comprehensive classification of retinal bipolar neurons by single-cell transcriptomics.  Cell, 2016; 166:1308-1323