title: Dual leucine zipper kinase regulates expression of axon guidance genes in mouse neuronal cells.
abstract: Recent genetic studies in model organisms, such as Drosophila, C. elegans and mice, have highlighted a critical role for dual leucine zipper kinase (DLK) in neural development and axonal responses to injury. However, exactly how DLK fulfills these functions remains to be determined. Using RNA-seq profiling, we evaluated the global changes in gene expression that are caused by shRNA-mediated knockdown of endogenous DLK in differentiated Neuro-2a neuroblastoma cells.
  
  
  
  Our analysis led to the identification of numerous up- and down-regulated genes, among which several were found to be associated with system development and axon guidance according to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, respectively. Because of their importance in axonal growth, pruning and regeneration during development and adult life, we then examined by quantitative RT-PCR the mRNA expression levels of the identified axon guidance genes in DLK-depleted cells. Consistent with the RNA-seq data, our results confirmed that loss of DLK altered expression of the genes encoding neuropilin 1 (Nrp1), plexin A4 (Plxna4), Eph receptor A7 (Epha7), Rho family GTPase 1 (Rnd1) and semaphorin 6B (Sema6b). Interestingly, this regulation of Nrp1 and Plxna4 mRNA expression by DLK in Neuro-2a cells was also reflected at the protein level, implicating DLK in the modulation of the function of these axon guidance molecules.
  
  
  
  Collectively, these results provide the first evidence that axon guidance genes are downstream targets of the DLK signaling pathway, which through their regulation probably modulates neuronal cell development, structure and function.
authors.affiliation: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 Boul. de l'Université, Sherbrooke, Québec, J1K 2R1, Canada.
authors.forename: Andréanne
authors.initials: A
authors.lastname: Blondeau
authors.affiliation: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 Boul. de l'Université, Sherbrooke, Québec, J1K 2R1, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Lucier
authors.affiliation: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 Boul. de l'Université, Sherbrooke, Québec, J1K 2R1, Canada.
authors.forename: Dominick
authors.initials: D
authors.lastname: Matteau
authors.affiliation: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 Boul. de l'Université, Sherbrooke, Québec, J1K 2R1, Canada.
authors.forename: Lauralyne
authors.initials: L
authors.lastname: Dumont
authors.affiliation: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 Boul. de l'Université, Sherbrooke, Québec, J1K 2R1, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Rodrigue
authors.affiliation: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 Boul. de l'Université, Sherbrooke, Québec, J1K 2R1, Canada.|Département d'informatique, Faculté des sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada.|Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Canada.
authors.forename: Pierre-Étienne
authors.initials: PÉ
authors.lastname: Jacques
authors.affiliation: Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 Boul. de l'Université, Sherbrooke, Québec, J1K 2R1, Canada. Richard.Blouin@USherbrooke.ca.
authors.forename: Richard
authors.identifier: 0000-0002-1882-3262
authors.initials: R
authors.lastname: Blouin
mesh_terms: D000818:Animals; D000071437:Axon Guidance / Q000235:genetics*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D034622:RNA Interference; D017423:Sequence Analysis, RNA; D015398:Signal Transduction
chemical_list: D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12
keywords: Axon guidance; DLK; Neurons