Fig. 8.

Crx>Math5 expression partially rescues RGC fate specification and optic nerve development in Math5 knockout (KO) mice. (A–C) Flatmounts of adult retinas from the indicated genotypes stained for TuJ1 (A, B) to mark axons, and Brn3a (C) to mark cell bodies of mature RGCs. In Math5 heterozygous mice (het), RGC axons fasciculate and project to the optic disc (OD), and their cell bodies are reactive for Brn3a. In Math5 KO mice, RGC axons are very sparse, meander and do not fasciculate, and their cell bodies not express Brn3a; and the presumptive optic disc (POD) is not fully developed. The Crx>Math5 Tg – and to a much lesser extent Crx>Math5 BAC – transgene is able to partially rescue RGC density (Brn3a+), pathfinding and fasciculation defects in Math5 KO mice. (D) Sections from adult retinas of the indicated genotypes, stained for GFP and Brn3a. In heterozygous mice, the Crx>Math5 Tg marks ~40% of the Brn3a+ RGC population. In contrast, rescued Brn3a+ RGCs derive exclusively from the Crx>Math5 Tg lineage (arrows). (E) Optic nerves of adult Math5 het and Crx>Math5 Tg; Math5 KO mice, stained with H+E. The rescued nerve is much thinner than the control. (F) Birthdating transgenic and control Math5 KO retinas. Pups were exposed to a pulse of BrdU at P1 and harvested at P22. Few, if any, GCL cells were labeled with BrdU in either genotype, indicating that rescued RGCs are born prior to P1. P, proximal; D, distal. Scale bar, 50 µm.