Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb

Motor neurons extend axons along specific trajectories, but the molecules t hat control their pathfinding remain poorly defined. We show that two LIM h omeodomain transcription factors, Lim1 and Lmx1b, control the initial traje ctory of motor axons in the developing mammalian limb. The expression of Li m1 by a lateral set of lateral motor column (LMC) neurons ensures that thei r axons select a dorsal trajectory in the limb. In a complementary manner, the expression of Lmx1b by dorsal limb mesenchymal cells controls the dorsa l and ventral axonal trajectories of medial and lateral LMC neurons. In the absence of these two proteins, motor axons appear to select dorsal and ven tral trajectories at random. Thus, LIM homeodomain proteins act within moto r neurons and cells that guide motor axons to establish the fidelity of a b inary choice in axonal trajectory.