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

Albert Pinhasov, Shmuel Mandel, Arkady Torchinsky, Eliezer Giladi, Zipora Pittel, Andrew M. Goldsweig, Stephen J. Servoss, Douglas E. Brenneman, Illana Gozes

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)83-90
Number of pages8
JournalDevelopmental Brain Research
Volume144
Issue number1
DOIs
StatePublished - Aug 12 2003
Externally publishedYes

Keywords

  • Activity-dependent neuroprotective protein
  • Embryo
  • Gene expression
  • Knockout
  • Neural tube
  • Vasoactive intestinal peptide

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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