title: Bone morphogenetic protein 2 inhibits neurite outgrowth of motor neuron-like NSC-34 cells and up-regulates its type II receptor.
abstract: Bone morphogenetic proteins (BMPs) regulate several aspects of neuronal behavior. For instance, BMP-2 has the ability to modulate, either positively or negatively, the outgrowth of neuronal processes in diverse cell types. In Drosophila motor neurons, the BMP type II receptor (BMPRII) homolog wishful thinking plays crucial roles on neuromuscular synaptogenesis signaling through Smad-dependent and Smad-independent pathways. However, a role for BMP signaling at the vertebrate neuromuscular junction has not been addressed. Herein, we have analyzed the expression of BMPRII and the effect of BMP-2 during the morphological differentiation of motor neuron-like NSC-34 cells. Our data indicate that BMPRII is up-regulated and becomes accumulated in somas and growth cones upon motor neuronal differentiation. BMP-2 inhibits the differentiation of NSC-34 cells, an effect that correlates with activation of a Smad-dependent pathway, induction of the inhibitory Id1 transcription factor, and down-regulation of the neurogenic factor Mash1. BMP-2 also activates effectors of Smad-independent pathways. Remarkably, BMP-2 treatment significantly increases the expression of BMPRII. Our findings provide the first evidence to suggest a role for BMP pathways on the differentiation of motor neurons leading to successful assembly and/or regeneration of the vertebrate neuromuscular synapse.
authors.affiliation: Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Benavente
authors.forename: Cristina
authors.initials: C
authors.lastname: Pinto
authors.forename: Margarita
authors.initials: M
authors.lastname: Parada
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Henríquez
authors.forename: Nelson
authors.initials: N
authors.lastname: Osses
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D006822:Hybrid Cells; D054461:Lim Kinases / Q000378:metabolism; D049410:Luciferases, Renilla / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000166:cytology*; D016501:Neurites / Q000187:drug effects*; D016900:Neurofilament Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D052006:Bone Morphogenetic Protein Receptors, Type II; D054461:Lim Kinases; D049410:Luciferases, Renilla; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; C499317:Ascl1 protein, mouse; C515893:Limk1 protein, mouse