Figure 8.

Egr3 has a role in target tissue innervation that is independent of axon guidance. A, Chemical clearing and whole-mount preparations using genetic axon tracing with DβH-Cre driver and StLa reporter mice made it possible to visualize a random subset of SCG neurons and their entire axon trajectories as they innervate the Smg. The Smg has profound innervation abnormalities in Egr3 KO mice (Eldredge et al., 2008) making this an informative preparation for testing whether innervation abnormalities are due to axon guidance defects or branching within the target tissue. B, Sparsely labeled axons were traced along the external carotid artery (eCA; white dashed lines) in Ctl (DβH-Cre⁺; Egr3^+/+; StLa^+/f) and Exp (DβH-Cre⁺; Egr3^−/−; StLa^+/f) mice. In both Ctl and Exp mice sympathetic axons coursed along the artery (arrowheads) to innervate the Smg, but occasional axons diverged from the artery to innervate tissues other than the Smg (arrow). There was no significant difference in the number of sympathetic axons traveling from the SCG to the Smg that diverged from the eCA between Ctl and Exp mice. C, In the Smg from Ctl and Exp mice lacZ-stained sympathetic axons entered the target tissue normally. However, the extent of axon branching within the target tissue was decreased in Exp relative to Ctl mice. *p < 0.015; N = 6–12 animals studied of each genotype as indicated. Scale bars: A, 500 μm; B, 250 μm; C, 100 μm. Dashed lines highlight the common carotid artery, internal carotid artery (iCA) and external carotid artery (eCA).