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[P251]: Organization of topographic motor axon projections by LIM homeodomain transcription factors’ control of expression of the EphB1 receptor tyrosine kinase and its ephrin‐B2 ligand
Author(s) -
Luria V.,
Jessell T.,
Laufer E.,
Kania A.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.309
Subject(s) - receptor tyrosine kinase , axon , homeobox , transcription factor , neuroscience , psychology , receptor , biology , genetics , gene
Myotopic topography is evident in the organisation of lateral motor column (LMC) motor neurons innervating the vertebrate limb. Medial LMC motor neurons innervate ventral limb muscles, while lateral LMC motor neurons innervate dorsal limb muscles. These axonal trajectories are controlled by the LIM homeodomain transcription factors Is1l and Lim1 expressed, respectively, by medial and lateral LMC motor neurons, and Lmx1b expressed in the dorsal limb mesenchyme. Within lateral LMC motor neurons, Lim1 controls the expression of EphA4, a receptor tyrosine kinase, while Lmx1b restricts ephrin-A ligand expression to the ventral limb, apparently leading to the choice of a dorsal axonal trajectory by repulsive mechanisms. However, EphA4 does not control the trajectory of medial LMC axons, raising the question of what molecular effectors control the ventral projection choice. We will present evidence that the EphB/ephrin-B signaling system directs medial LMC projections to ventral limb mesenchyme. The receptor tyrosine kinase EphB1 is selectively expressed by medial LMC motor neurons, while ephrin-B ligands are enriched within the dorsal limb mesenchyme. Based on gain and loss of function experiments, Isl1, Lim1 and Lmx1b appear to control the distribution of EphB1 and its ligands. These data suggest that the interaction of EphB1 on medial LMC motor axons with ephrin-B ligands in the dorsal limb mesenchyme directs medial LMC motor axons into the ventral limb via a repulsive mechanism. Consistent with this hypothesis, an EphB1 null mutation results in misrouting of medial LMC motor axons into the dorsal limb. We are currently examining the effect on the dorsoventral projection choice of overexpressing EphB1 in lateral LMC motor axons, as well as the interactions between Lim1 and Isl1 that coordinate expression of EphA4 in lateral LMC motor neurons, and EphB1 in medial LMC motor neurons.