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

Autor: Shmuel Mandel, Eliezer Giladi, Douglas E. Brenneman, Andrew M. Goldsweig, Stephen J. Servoss, Zipora Pittel, Illana Gozes, Albert Pinhasov, Arkady Torchinsky
Rok vydání: 2003
Předmět:
Time Factors
PAX6 Transcription Factor
Blotting
Western
Molecular Sequence Data
Gestational Age
Nerve Tissue Proteins
Biology
Neuroprotection
Embryonic and Fetal Development
Mice
Organ Culture Techniques
Developmental Neuroscience
Gene expression
medicine
Animals
Paired Box Transcription Factors
RNA
Messenger
Cloning
Molecular
Eye Proteins
In Situ Hybridization
Homeodomain Proteins
Mice
Knockout
Regulation of gene expression
Reverse Transcriptase Polymerase Chain Reaction
Embryogenesis
Neural tube
Brain
Gene Expression Regulation
Developmental
Embryo
Blotting
Northern
Embryo
Mammalian
Molecular biology
Cell biology
DNA-Binding Proteins
Mice
Inbred C57BL
Repressor Proteins
medicine.anatomical_structure
embryonic structures
Knockout mouse
PAX6
Octamer Transcription Factor-3
Transcription Factors
Vasoactive Intestinal Peptide
Developmental Biology
Zdroj: Developmental Brain Research. 144:83-90
ISSN: 0165-3806
DOI: 10.1016/s0165-3806(03)00162-7
Popis: 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.
Databáze: OpenAIRE
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