title: Latent process genes for cell differentiation are common decoders of neurite extension length.
abstract: A latent process involving signal transduction and gene expression is needed as a preparation step for cellular function. We previously found that nerve growth factor (NGF)-induced cell differentiation has a latent process, which is dependent on ERK activity and gene expression and required for subsequent neurite extension. A latent process can be considered as a preparation step that decodes extracellular stimulus information into cellular functions; however, molecular mechanisms of this process remain unknown. We identified Metrnl, Dclk1 and Serpinb1a as genes that are induced during the latent process (LP) with distinct temporal expression profiles and are required for subsequent neurite extension in PC12 cells. The LP genes showed distinct dependency on the duration of ERK activity, and they were also induced during the latent process of PACAP- and forskolin-induced cell differentiation. Regardless of neurotrophic factors, expression levels of the LP genes during the latent process (0-12 hours), but not phosphorylation levels of ERK, always correlated with subsequent neurite extension length (12-24 hours). Overexpression of all LP genes together, but not of each gene separately, enhanced NGF-induced neurite extension. The LP gene products showed distinct spatial localization. Thus, the LP genes appear to be the common decoders for neurite extension length regardless of neurotrophic factors, and they might function in distinct temporal and spatial manners during the latent process. Our findings provide molecular insight into the physiological meaning of the latent process as the preparation step for decoding information for future phenotypic change.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Akimoto
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Yugi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Uda
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Chung
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakamuta
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: Shinya
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D005576:Colforsin / Q000494:pharmacology; D000089742:Doublecortin-Like Kinases; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
chemical_list: C546969:Metrn protein, rat; D009419:Nerve Tissue Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D015843:Serpins; D005576:Colforsin; D020932:Nerve Growth Factor; D000089742:Doublecortin-Like Kinases; C485526:Dclk1 protein, rat; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases