title: The bone morphogenetic protein roof plate chemorepellent regulates the rate of commissural axonal growth.
abstract: Commissural spinal axons extend away from the roof plate (RP) in response to a chemorepellent mediated by the bone morphogenetic proteins (BMPs). Previous studies have focused on the ability of commissural axons to translate a spatial gradient of BMPs into directional information in vitro. However, a notable feature of this system in vivo is that the gradient of BMPs is thought to act from behind the commissural cell bodies, making it possible for the BMPs to have a continued effect on commissural axons as they grow away from the RP. Here, we demonstrate that BMPs activate the cofilin regulator Lim domain kinase 1 (Limk1) to control the rate of commissural axon extension in the dorsal spinal cord. By modulating Limk1 activity in both rodent and chicken commissural neurons, the rate of axon growth can either be stalled or accelerated. Altering the activation state of Limk1 also influences subsequent guidance decisions: accelerated axons make rostrocaudal projection errors while navigating their intermediate target, the floor plate. These results suggest that guidance cues can specify information about the rate of growth, to ensure that axons reach subsequent signals either at particular times or speeds during development.
authors.affiliation: Neuroscience Graduate Program, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Phan
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Hazen
authors.forename: Michele
authors.initials: M
authors.lastname: Frendo
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Butler
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D019556:COS Cells; D002478:Cells, Cultured; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D054461:Lim Kinases / Q000502:physiology*; D051379:Mice; D009434:Neural Pathways / Q000254:growth & development; D051381:Rats; D013997:Time Factors
chemical_list: D019485:Bone Morphogenetic Proteins; D054461:Lim Kinases; C515893:Limk1 protein, mouse