Coordinate Roles for LIM Homeobox Genes in Directing the Dorsoventral Trajectory of Motor Axons in the Vertebrate Limb

• Published in: Cell 2000-07, Vol.102 (2), p.161-173
• Main Authors: Kania, Artur, Johnson, Randy L, Jessell, Thomas M
• Format: Article
• Language: English
• Subjects: Animals; axons; Axons - physiology; Cells, Cultured; Extremities - embryology; Extremities - innervation; Female; Gene Expression Regulation, Developmental; Genes, Homeobox; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Homeodomain Proteins - physiology; Lac Operon; LIM domain proteins; LIM-Homeodomain Proteins; Lim1 protein; Lmx1b protein; Male; Mice; motor neurons; Motor Neurons - physiology; Transcription Factors; Vertebrates
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)00022-2

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