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Originally published In Press as doi:10.1074/jbc.M007097200 on September 19, 2000
J. Biol. Chem., Vol. 275, Issue 50, 39662-39670, December 15, 2000
Myocyte Enhancer Factors-2B and -2C Are Required for Adhesion
Related Kinase Repression of Neuronal Gonadotropin Releasing Hormone
Gene Expression*
Melissa P.
Allen §,
Mei
Xu §,
Chan
Zeng §,
Stuart A.
Tobet¶, and
Margaret E.
Wierman § **
From the Department of Medicine and Physiology
and Biophysics, University of Colorado Health Sciences Center, Denver,
Colorado 80262, the § Research Service, Veterans Affairs
Medical Center, Denver, Colorado 80220, and the ¶ Program in
Neuroscience, The Shriver Center, Harvard Medical School,
Waltham, Massachusetts 02452
Synthesis of the hypothalamic peptide,
gonadotropin releasing hormone (GnRH), is paramount for reproductive
function. GnRH neurons originate in the olfactory region and migrate
into the forebrain during development. We recently implicated adhesion related kinase (Ark) in GnRH neuron development based on its
differential expression in two GnRH producing cell lines, GT1-7 and
Gn10. The Ark membrane receptor encodes an extracellular domain
resembling cell adhesion molecules and an intracellular tyrosine
kinase. Ark is expressed in Gn10 cells derived from migrating GnRH
neurons but not GT1-7 cells of the post-migratory phenotype.
Here, we show that Ark and GnRH transcripts are colocalized in the
cribriform plate at midgestation, suggesting that Ark is expressed in
migrating GnRH neurons in vivo. Furthermore, we have
identified the GnRH gene as a downstream target of Ark signaling. Ark
inhibits GnRH gene expression in GnRH neuronal cells via the
coordinated binding of myocyte enhancer factor-2B and -2C (MEF-2B and
-2C) and a putative homeoprotein within the proximal rat GnRH promoter.
Given that MEF-2 proteins are widely expressed in the brain, these
studies provide further evidence for MEF-2 action during neuronal
development. Moreover, our studies elucidate a potential role for Ark
in regulating GnRH gene expression during GnRH neuronal migration.
*
This work was supported by National Institute of Child
Health and Human Development Grants HD31191-03 (to M. E. W.), HD33441 (to G. Schwarting and S. A. T.), and a
Lalor Fellowship (to M. P. A.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
**
To whom correspondence should be addressed: Veterans Affairs
Medical Center, Box 111H, 1055 Clermont St., Denver, CO 80220. Tel:
303-399-8020 (ext. 3137); Fax: 303-393-5271; E-mail:
margaret.wierman@uchsc.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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