This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kramer, P. R. Articles by Wray, S. Search for Related Content PubMed PubMed Citation Articles by Kramer, P. R. Articles by Wray, S.

Transcription Factor Activator Protein-2 Is Required for Continued Luteinizing Hormone-Releasing Hormone Expression in the Forebrain of Developing Mice

Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health (P.R.K., S.W.), Bethesda, Maryland 20892; and Department of Biochemistry and Molecular Biology, Pennsylvania State University (R.K., P.J.M.), University Park, Pennsylvania 16302

Address all correspondence and requests for reprints to: Dr. Susan Wray, Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 36, Room 5A-25, Bethesda, Maryland 20895-4156. E-mail: swray{at}codon.nih.gov

LHRH is the neuropeptide responsible for reproductive function. Prenatally, LHRH expression begins when neurons are in the olfactory pit and continues as these cells migrate into the brain. Thus, LHRH neurons maintain neuropeptide expression through very distinct environments. The regulatory interactions that control onset and continued expression of the LHRH phenotype are unknown. To begin to address this question primary LHRH neurons were removed from nasal explants at different ages. A complementary DNA (cDNA) subtraction screen was performed comparing a 3.5-days in vitro LHRH neuron [approximately embryonic day 15 (E15) in vivo] to two 10.5-days in vitro LHRH neurons (approximately postnatal day 1 in vivo). The transcription factor activator protein-2 (AP-2) was differentially expressed and was present in the developmentally younger LHRH neuron. In vivo analysis revealed that LHRH neurons expressed AP-2 as they migrated across the cribriform plate and into the forebrain beginning on E13.5, but that coexpression of LHRH and AP-2 was no longer detected in postnatal day 1 animals. This suggested a regulatory role for AP-2 in LHRH neurons. Analysis of animals lacking AP-2 revealed a dramatic decrease in forebrain LHRH neurons between E13.5 and E14.5, correlating with normal onset of AP-2 expression in LHRH neurons as they entered the central nervous system. Nasal cells robustly expressing LHRH were still present on E14.5. The continued presence of forebrain LHRH cells is proposed based on a second marker, galanin, and lack of increased apoptotic/necrotic cells in this region. A decrease in LHRH messenger RNA in forebrain neurons indicates regulation of LHRH occurred at the transcriptional or posttranscriptional level in mutant animals. These results indicate a developmentally restricted involvement of the transcription factor AP-2 in LHRH expression once the LHRH neurons have migrated into the forebrain, but before establishment of an adult-like distribution.

This article has been cited by other articles:

				S. Constantin and S. Wray Gonadotropin-Releasing Hormone-1 Neuronal Activity Is Independent of Hyperpolarization-Activated Cyclic Nucleotide-Modulated Channels but Is Sensitive to Protein Kinase A-Dependent Phosphorylation Endocrinology, July 1, 2008; 149(7): 3500 - 3511. [Abstract] [Full Text] [PDF]

				S. Constantin and S. Wray Gonadotropin-Releasing Hormone-1 Neuronal Activity Is Independent of Cyclic Nucleotide-Gated Channels Endocrinology, January 1, 2008; 149(1): 279 - 290. [Abstract] [Full Text] [PDF]

				P. Giacobini, A. Messina, S. Wray, C. Giampietro, T. Crepaldi, P. Carmeliet, and A. Fasolo Hepatocyte Growth Factor Acts as a Motogen and Guidance Signal for Gonadotropin Hormone-Releasing Hormone-1 Neuronal Migration J. Neurosci., January 10, 2007; 27(2): 431 - 445. [Abstract] [Full Text] [PDF]

				P. Giacobini and S. Wray Cholecystokinin Directly Inhibits Neuronal Activity of Primary Gonadotropin-Releasing Hormone Cells through Cholecystokinin-1 Receptor Endocrinology, January 1, 2007; 148(1): 63 - 71. [Abstract] [Full Text] [PDF]

				M. L. Givens, N. Rave-Harel, V. D. Goonewardena, R. Kurotani, S. E. Berdy, C. H. Swan, J. L. R. Rubenstein, B. Robert, and P. L. Mellon Developmental Regulation of Gonadotropin-releasing Hormone Gene Expression by the MSX and DLX Homeodomain Protein Families J. Biol. Chem., May 13, 2005; 280(19): 19156 - 19165. [Abstract] [Full Text] [PDF]

				J. C. Gill, S. M. Moenter, and P.-S. Tsai Developmental Regulation of Gonadotropin-Releasing Hormone Neurons by Fibroblast Growth Factor Signaling Endocrinology, August 1, 2004; 145(8): 3830 - 3839. [Abstract] [Full Text] [PDF]

				P. Giacobini, A. S. Kopin, P. M. Beart, L. D. Mercer, A. Fasolo, and S. Wray Cholecystokinin Modulates Migration of Gonadotropin-Releasing Hormone-1 Neurons J. Neurosci., May 19, 2004; 24(20): 4737 - 4748. [Abstract] [Full Text] [PDF]

				J. P. Moore Jr, E. Shang, and S. Wray In Situ GABAergic Modulation of Synchronous Gonadotropin Releasing Hormone-1 Neuronal Activity J. Neurosci., October 15, 2002; 22(20): 8932 - 8941. [Abstract] [Full Text] [PDF]

				N. Sharifi, A. E. Reuss, and S. Wray Prenatal LHRH Neurons in Nasal Explant Cultures Express Estrogen Receptor {beta} Transcript Endocrinology, July 1, 2002; 143(7): 2503 - 2507. [Abstract] [Full Text] [PDF]

				I Monge, R Krishnamurthy, D Sims, F Hirth, M Spengler, L Kammermeier, H Reichert, and P. Mitchell Drosophila transcription factor AP-2 in proboscis, leg and brain central complex development Development, January 4, 2001; 128(8): 1239 - 1252. [Abstract] [PDF]

				P.R. Kramer and S. Wray Novel gene expressed in nasal region influences outgrowth of olfactory axons and migration of luteinizing hormone-releasing hormone (LHRH) neurons Genes & Dev., July 15, 2000; 14(14): 1824 - 1834. [Abstract] [Full Text]