TY - JOUR
T1 - Activity-dependent neuroprotective protein
T2 - A novel gene essential for brain formation
AU - Pinhasov, Albert
AU - Mandel, Shmuel
AU - Torchinsky, Arkady
AU - Giladi, Eliezer
AU - Pittel, Zipora
AU - Goldsweig, Andrew M.
AU - Servoss, Stephen J.
AU - Brenneman, Douglas E.
AU - Gozes, Illana
N1 - Funding Information:
We thank Dr. H. Westphal, Dr A. Tomac, Dr M. Mukhopadhyay, Dr E. Lee, Dr Z. Nevo, Dr M. Weil, Dr A.D. Spier, S.P. Huang, N. Posternak, S. Furman, A. Grinberg and A. Pinchasov for their invaluable help. This work was supported in part by the Institute for the Study of Aging, the United States–Israel Binational Science Foundation and the Neufeld Memorial Award, (to IG and DEB), by the Israel Science Foundation, The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, by the Dr Diana and Zyga Elton Fund, NICHD intramural and Allon Therapeutics, Inc. Patents have been applied for ADNP. Albert Pinhasov and Shmuel Mandel performed this work in partial fulfillment of the PhD requirements at Tel Aviv University.
PY - 2003/8/12
Y1 - 2003/8/12
N2 - 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.
AB - 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.
KW - Activity-dependent neuroprotective protein
KW - Embryo
KW - Gene expression
KW - Knockout
KW - Neural tube
KW - Vasoactive intestinal peptide
UR - http://www.scopus.com/inward/record.url?scp=0042347559&partnerID=8YFLogxK
U2 - 10.1016/S0165-3806(03)00162-7
DO - 10.1016/S0165-3806(03)00162-7
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C2 - 12888219
AN - SCOPUS:0042347559
SN - 0165-3806
VL - 144
SP - 83
EP - 90
JO - Developmental Brain Research
JF - Developmental Brain Research
IS - 1
ER -