Cited by 239Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationFetal and Pediatric Neurological Disorders

Activity-dependent neuroprotective protein: a novel gene essential for brain formation

Pinhasov, Albert, Mandel, Shmuel, Torchinsky, Arkady, Giladi, Eliezer, Pittel, Zipora, Goldsweig, Andrew M, Servoss, Stephen J, Brenneman, Douglas E +1 more·2003·Developmental Brain Research

Abstract

We have recently cloned the novel homeobox-containing activity-dependent neuroprotective protein (ADNP). In the current study, mouse ADNP was shown to be expressed at the time of neural tube closure, detected at E7.5 and increased on E9.5. Expression was augmented in the brain (E12.5), sustained throughout embryogenesis and regulated by VIP. To assess the function of ADNP, knockout mice were established. Detailed analysis revealed cranial neural tube closure failure and death on E8.5-9.0 of the ADNP-knockout embryos. The expression of Oct4, a gene associated with germ-line maintenance was markedly augmented in the knockout embryos. In contrast, the expression of Pax6, a gene crucial for cerebral cortex formation, was abolished in the brain primordial tissue of the knockout embryos. Thus, Pax6 and Oct4 constitute a part of the mechanism of action of ADNP on brain formation, inhibiting germ-line division while activating morphogenesis. In conclusion, ADNP is identified here as a new key gene essential for organogenesis in the developing embryo and may be implicated as a clinical target associated with proper neurodevelopment.

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Crossref · 10.1016/s0165-3806(03)00162-7

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Authors
Pinhasov, A., Mandel, S., Torchinsky, A., Giladi, E., Pittel, Z., Goldsweig, A. M., Servoss, S. J., Brenneman, D. E., & Gozes, I.
Affiliations
  • Tel Aviv University (IL)
  • National Institutes of Health (US)
Corresponding author
Gozes, Illana
Venue
Developmental Brain Research
Publisher
Elsevier BV
Published
2003-08
Volume
144
Issue
1
Pages
83-90
ISSN
0165-3806 (ISSN-L)
OpenAlex
W2001381614
Cited by
239
References
33
Citations by year
2026: 13 · 2025: 12 · 2024: 13 · 2023: 10 · 2022: 11 · 2021: 8 · 2020: 16 · 2019: 14 · 2018: 12 · 2017: 9 · 2016: 12 · 2015: 10 · 2014: 10 · 2013: 11 · 2012: 8
FWCI
2.28
Type
journal article
Language
en
Open access
closed
Locations
  • Developmental Brain Research (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
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
Keywords
ADNP, homeobox genes, neural tube closure, brain development, Pax6, Oct4, organogenesis
MeSH terms
PAX6 Transcription Factor, Animals, Brain, Cloning, Molecular, DNA-Binding Proteins, Embryo, Mammalian, Eye Proteins, Embryonic and Fetal Development, Gestational Age, Mice, Inbred C57BL, Molecular Sequence Data, Nerve Tissue Proteins, Organ Culture Techniques, Repressor Proteins, RNA, Messenger, Time Factors, Transcription Factors, Vasoactive Intestinal Peptide, Blotting, Northern, Blotting, Western, In Situ Hybridization, Mice, Knockout, Homeodomain Proteins, Gene Expression Regulation, Developmental, Reverse Transcriptase Polymerase Chain Reaction, Octamer Transcription Factor-3, Mice, Paired Box Transcription Factors

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