title: ADNP differential nucleus/cytoplasm localization in neurons suggests multiple roles in neuronal differentiation and maintenance.
abstract: Complete deficiency in activity-dependent neuroprotective protein (ADNP) results in neural tube closure defects and death at gestation day 9 in mice. ADNP-deficient embryos exhibit dramatic increases in gene transcripts associated with lipid metabolism coupled to reduction in organogenesis/neurogenesis-related transcripts. In the pluripotent teratocarcinoma cell line P19, ADNP was shown to interact with specific chromatin regions in the neurodifferentiated state, which was associated with binding to the heterochromatin protein 1 alpha. In this study, using P19 cells as a differentiation model, we showed that ADNP expression and cytoplasm/nucleus distribution is unique in neuronal-differentiated cells compared to cardiovascular and nondifferentiated pluripotent cells. ADNP-like immunohistochemical localization to the neuronal cytoplasm and neurites was shown in this study not only in the cellular model but also in the brain cerebral cortex and olfactory bulb. Small hairpin RNA ADNP downregulation was used to further investigate ADNP involvement in p19 neurodifferentiation. An approximately 80% robust reduction in ADNP led to a substantial reduction in embryoid body formation and a significant reduction (approximately 50%) in neurite numbers. These results position ADNP in direct association with neuronal cell differentiation and maturation.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Medical School, Tel Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Mandel
authors.forename: Irit
authors.initials: I
authors.lastname: Spivak-Pohis
authors.forename: Illana
authors.initials: I
authors.lastname: Gozes
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology*; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology; D034622:RNA Interference
chemical_list: C117632:Adnp protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins