title: Type Ib BMP receptors mediate the rate of commissural axon extension through inhibition of cofilin activity.
abstract: Bone morphogenetic proteins (BMPs) have unexpectedly diverse activities establishing different aspects of dorsal neural circuitry in the developing spinal cord. Our recent studies have shown that, in addition to spatially orienting dorsal commissural (dI1) axons, BMPs supply 'temporal' information to commissural axons to specify their rate of growth. This information ensures that commissural axons reach subsequent signals at particular times during development. However, it remains unresolved how commissural neurons specifically decode this activity of BMPs to result in their extending axons at a specific speed through the dorsal spinal cord. We have addressed this question by examining whether either of the type I BMP receptors (Bmpr), BmprIa and BmprIb, have a role controlling the rate of commissural axon growth. BmprIa and BmprIb exhibit a common function specifying the identity of dorsal cell fate in the spinal cord, whereas BmprIb alone mediates the ability of BMPs to orient axons. Here, we show that BmprIb, and not BmprIa, is additionally required to control the rate of commissural axon extension. We have also determined the intracellular effector by which BmprIb regulates commissural axon growth. We show that BmprIb has a novel role modulating the activity of the actin-severing protein cofilin. These studies reveal the mechanistic differences used by distinct components of the canonical Bmpr complex to mediate the diverse activities of the BMPs.
authors.affiliation: Neuroscience Graduate Program, HNB 201, 3641 Watt Way, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Supraja G
authors.initials: SG
authors.lastname: Varadarajan
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Li
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Butler
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism*; D002642:Chick Embryo; D051338:Cofilin 1 / Q000378:metabolism*; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry / Q000379:methods; D054461:Lim Kinases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D013116:Spinal Cord; D013997:Time Factors
chemical_list: D051338:Cofilin 1; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I