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.
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A role for ADNP in neuronal cell differentiation and maturation was suggested by a study observing decreased embryoid body number and size and fewer neurites after ADNP knockdown with shRNA in P19 cells.
“A role in neuronal cell differentiation and maturation was suggested after observing a substantial decrease in the number and size of embryoid bodies and the number of neurites after knockdown of ADNP with shRNA in P19 cells17.”
From A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP (2014) · cites this paper as [17]
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A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP
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Activity-Dependent Neuroprotective Protein Modulates Its Own Gene Expression
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- Authors
- Mandel, S., Spivak-Pohis, I., & Gozes, I.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Gozes, Illana
- ORCID
- Gozes, Illana
- Venue
- Journal of Molecular Neuroscience
- Published
- 2008-02-20
- Volume
- 35
- Issue
- 2
- Pages
- 127-141
- ISSN
- 0895-8696 (ISSN-L)
- 1559-1166
- OpenAlex
- W2078990638
- Cited by
- 91
- References
- 34
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 15 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 3 · 2012: 3
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- ADNP, neuronal differentiation, subcellular localization, P19 cells, neurite formation, embryoid body formation, neural tube defects, neurogenesis, cerebral cortex, olfactory bulb, small hairpin RNA knockdown
- MeSH terms
- Animals, Cardiovascular System, Cell Differentiation, Cell Nucleus, Cerebral Cortex, Cytoplasm, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Neurons, Olfactory Bulb, Neurites, Homeodomain Proteins, Gene Expression Regulation, Developmental, RNA Interference, Pluripotent Stem Cells, Cell Line, Tumor, Mice, Embryonal Carcinoma Stem Cells
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