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Math5(Atoh7) gene dosage limits retinal ganglion cell genesis

Prasov, Lev; Nagy, Melinda; Rudolph, Dellaney D.; Glaser, Tom

Vision, Retina

The basic helix–loop–helix factor Math5 (Atoh7) is critical for the determination of retinal ganglion cell (RGC) fate in mice. Recently, genome-wide association studies have identified the ATOH7 locus as a major determinant of variation in the human optic disc area, which is directly correlated with the RGC number. These studies suggest that the level of Math5 expression may determine the ultimate number of RGCs. To test this hypothesis, we systematically compared optic nerve area and RGC axon number in C57BL/6J congenic Math5 +/- and +/+ mice at young adult and neonatal ages by transmission electron microscopy. Optic disc area and RGC abundance were not significantly different in adults, but heterozygotes had thinner optic nerves and 25–30% fewer RGCs at birth than wild-type littermates ( P <0.05). Our results suggest that Math5 dosage is important for the genesis, but not the ultimate number, of RGCs. Our findings highlight the importance of ganglion cell culling as a compensatory mechanism for retinal homeostasis, and support a quantitative role for Math5 in RGC specification.

Departments of Human Genetics and Internal Medicine, University of Michigan Medical Center, University of Michigan, Ann Arbor, Michigan, USA

Correspondence to Tom Glaser, Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, One Shields Avenue, Davis CA 95616, USA e-mail:,

Received May 10, 2012

accepted May 15, 2012

© 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins