title: Functional whole-genome analysis identifies Polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator alphaB-crystallin.
abstract: This study aimed at identifying transcriptional changes associated to neuronal differentiation induced by six distinct stimuli using whole-genome microarray hybridization analysis. Bioinformatics analyses revealed the clustering of these six stimuli into two categories, suggesting separate gene/pathway dependence. Treatment with specific inhibitors demonstrated the requirement of both Janus kinase and microtubule-associated protein kinase activation to trigger differentiation with nerve growth factor (NGF) and dibutyryl cAMP. Conversely, activation of protein kinase A, phosphatidylinositol-3-kinase alpha, and mammalian target of rapamycin, although required for dibutyryl cAMP-induced differentiation, exerted a negative feedback on NGF-induced differentiation. We identified Polo-like kinase 2 (Plk2) and poliovirus receptor (PVR) as indispensable for NGF-driven neuronal differentiation and alphaB-crystallin (Cryab) as an inhibitor of this process. Silencing of Plk2 or PVR blocked NGF-triggered differentiation and Cryab down-regulation, while silencing of Cryab enhanced NGF-induced differentiation. Our results position both Plk2 and PVR upstream of the negative regulator Cryab in the pathway(s) leading to neuronal differentiation triggered by NGF.
authors.affiliation: Departments of Target Research, Merck Serono International S.A. 9, Chemin de Mines, 1202 Geneva, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Draghetti
authors.forename: Catherine
authors.initials: C
authors.lastname: Salvat
authors.forename: Francisca
authors.initials: F
authors.lastname: Zanoguera
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Curchod
authors.forename: Chloé
authors.initials: C
authors.lastname: Vignaud
authors.forename: Helene
authors.initials: H
authors.lastname: Peixoto
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Cara
authors.forename: David
authors.initials: D
authors.lastname: Fischer
authors.forename: Mohanraj
authors.initials: M
authors.lastname: Dhanabal
authors.forename: Goutopoulos
authors.initials: G
authors.lastname: Andreas
authors.forename: Hadi
authors.initials: H
authors.lastname: Abderrahim
authors.forename: Christian
authors.initials: C
authors.lastname: Rommel
authors.forename: Montserrat
authors.initials: M
authors.lastname: Camps
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D019295:Computational Biology; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D011991:Receptors, Virus; D038203:alpha-Crystallin B Chain; C066100:poliovirus receptor; D020932:Nerve Growth Factor; D017346:Protein Serine-Threonine Kinases; C530504:Plk2 protein, rat
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