Document Detail


Activity-dependent neuroprotective protein: a novel gene essential for brain formation.
MedLine Citation:
PMID:  12888219     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Albert Pinhasov; Shmuel Mandel; Arkady Torchinsky; Eliezer Giladi; Zipora Pittel; Andrew M Goldsweig; Stephen J Servoss; Douglas E Brenneman; Illana Gozes
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research. Developmental brain research     Volume:  144     ISSN:  0165-3806     ISO Abbreviation:  Brain Res. Dev. Brain Res.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-07-30     Completed Date:  2003-10-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8908639     Medline TA:  Brain Res Dev Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  83-90     Citation Subset:  IM    
Affiliation:
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Northern / methods
Blotting, Western / methods
Brain / embryology*,  metabolism
Cloning, Molecular
DNA-Binding Proteins / metabolism
Embryo, Mammalian
Embryonic and Fetal Development*
Eye Proteins
Gene Expression Regulation, Developmental*
Gestational Age
Homeodomain Proteins / metabolism
In Situ Hybridization / methods
Mice
Mice, Inbred C57BL
Mice, Knockout / embryology,  genetics,  metabolism
Molecular Sequence Data
Nerve Tissue Proteins / genetics,  metabolism*,  physiology
Octamer Transcription Factor-3
Organ Culture Techniques / methods
Paired Box Transcription Factors
RNA, Messenger / biosynthesis,  drug effects
Repressor Proteins
Reverse Transcriptase Polymerase Chain Reaction / methods
Time Factors
Transcription Factors*
Vasoactive Intestinal Peptide / pharmacology
Chemical
Reg. No./Substance:
0/Adnp protein, mouse; 0/DNA-Binding Proteins; 0/Eye Proteins; 0/Homeodomain Proteins; 0/Nerve Tissue Proteins; 0/Octamer Transcription Factor-3; 0/PAX6 protein; 0/Paired Box Transcription Factors; 0/Pou5f1 protein, mouse; 0/RNA, Messenger; 0/Repressor Proteins; 0/Transcription Factors; 37221-79-7/Vasoactive Intestinal Peptide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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