RESUMEN
Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/-) mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley's social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders.
RESUMEN
In the developing retina, neurogenesis and cell differentiation are coupled with cell proliferation. However, molecular mechanisms that coordinate cell proliferation and differentiation are not fully understood. In this study, we found that retinal neurogenesis is severely delayed in the zebrafish stem-loop binding protein (slbp) mutant. SLBP binds to a stem-loop structure at the 3'-end of histone mRNAs, and regulates a replication-dependent synthesis and degradation of histone proteins. Retinal cell proliferation becomes slower in the slbp1 mutant, resulting in cessation of retinal stem cell proliferation. Although retinal stem cells cease proliferation by 2 days postfertilization (dpf) in the slbp mutant, retinal progenitor cells in the central retina continue to proliferate and generate neurons until at least 5dpf. We found that this progenitor proliferation depends on Notch signaling, suggesting that Notch signaling maintains retinal progenitor proliferation when faced with reduced SLBP activity. Thus, SLBP is required for retinal stem cell maintenance. SLBP and Notch signaling are required for retinal progenitor cell proliferation and subsequent neurogenesis. We also show that SLBP1 is required for intraretinal axon pathfinding, probably through morphogenesis of the optic stalk, which expresses attractant cues. Taken together, these data indicate important roles of SLBP in retinal development.
Asunto(s)
Proteínas de Unión al ARN/biosíntesis , Receptores Notch/metabolismo , Retina/embriología , Pez Cebra/embriología , Animales , Diferenciación Celular , Proliferación Celular , Quimiocina CXCL12/biosíntesis , Proteínas Fluorescentes Verdes , Histonas/genética , Mutación , Neurogénesis , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteínas de Unión al ARN/genética , Retina/citología , Transducción de Señal/genética , Células Madre , Ubiquitina-Proteína Ligasas/genética , Proteínas de Pez Cebra/biosíntesis , Proteínas de Pez Cebra/genéticaRESUMEN
Sugar analysis by postcolumn labeling using phenylhydrazine with high-performance liquid chromatography is herein introduced. Phenylhydrazine reacts not only with the reducing end of oligosaccharides, but also with mono-sugar components with degraded glycosyl bonds. N-acethylhexosamine is highly sensitive at a sub-pico molecular range, and this method is useful for detecting glycans on glycoproteins. The detection limit of fetuin, a protein possessing 3 N-glycans and 3 O-glycans, was 0.17 pmol by infusion analysis, and chromatograms of glycopeptides separated on an ODS column were obtained. These results suggest that this method is useful for the preparation of glycopeptides for glyco-proteomics research.