Cell Biology of Neurons, Muscle and Glia; Clinical Neuroscience; Neural Development and Plasticity; and Neuroendocrinology
Dr. Wray received her B.A. degree from Middlebury College and her M.S, and Ph.D. degrees from University of Rochester School of Medicine & Dentistry where she worked on development of neuroendocrine systems associated with puberty. She continued her work on neuroendocrine systems as a postdoctoral fellow with Harold Gainer in NICHD. In 1992 she became a faculty member of NINDS as a Unit Chief in the Laboratory of Neurochemistry and in 1999 became Chief of the newly created Cellular and Developmental Neurobiology Section. She is a council member of the International Society of Neuroendocrinology and a founding member of the American Neuroendocrine Society. Dr. Wray's laboratory is studying developmental cues underlying neuronal migration, and neurogenesis and regulation of neuroendocrine cells essential for reproduction.
Research Interests:
The Cellular and Developmental Neurobiology Section (CDNS), conducts fundamental research on neurogenesis of placodally derived neurons and the system dynamics of these cells which allow them to exhibit synchronized behavior. Our focus is on development and regulation of GnRH neurons, cells essential for reproduction. GnRH neurons originate in the nasal placode and during prenatal development migrate into the brain. Once within the brain, GnRH neurons become integral components of the hypothalamic-pituitary-gonadal axis and exhibit pulses of GnRH secretion in reproductively mature animals. Alterations in normal development or regulation of the GnRH system results in reproductive dysfunctions, as is seen in patients with Kallman Syndrome.
Our research addresses critical neurobiological issues such as phenotypic commitment and mechanisms involved in neuronal migration. Projects focus on craniofacial development, differentiation and migration of GnRH cells, and olfactory axon outgrowth. This system is a model for neurons exhibiting axophilic migration. Research includes:
- signals for proper craniofacial development,
- guidance factors that modulate neuronal migration, and
- intracellular signaling controlling cell movement and corresponding changes in cytoskeletal elements.
In addition, the mechanisms regulating GnRH neuronal activity, including peptide secretion are being examined to decipher the cellular characteristics underlying neuroendocrine function and pulsatile secretion. We take advantage of the physiology of the GnRH system by examining the molecular and cellular properties of GnRH neuronal activity at different developmental, metabolic and/or reproductive states.
Research models include nasal explants, slice cultures, immortalized GnRH cell lines, and normal, cre/lox and transgenic mice. Approaches include videomicroscopy, calcium imaging, electrophysiology, immunocytochemistry, in situ histochemistry, single-cell PCR, and subtractive cDNA screening. Together, these models and approaches are used to manipulate the GnRH system.
Lab Members:
Postdoctoral Fellows
- Dr. Maleeha Akram
- Dr. Naira Mansano
- Dr. Clarisse Quigon
Postbaccalaureate Fellows
- Hannah Bow
- Jessica Kearny
Graduate Student NIH/Karolinska Program
- Jacob Short
Selected Publications:
2023
Cho H-J, Gurbuz F, Stamou M, Kotan LD, Farmer SM, Can S, Tompkins MF, Mamadova J, Altincik SA, Gokce C, Catli G, Bugrul F, Bartlett K, Turan I, Balasubramanian R, Yuksel B, Seminara SB, Wray S, Topaloglu AK. POU6F2 mutation in humans with pubertal failure alters GnRH transcript expression. Frontiers in Endocrinology: Pediatric Endocrinology, 2023.
Shostak D, Constantin S, Flannery J, Wray S. Acetylcholine regulation of GnRH neuronal activity: A circuit in the medial septum, Frontiers in Endocrinology: Neuroendocrine Science, 2023.
Constantin S, Sokanovic S, Mochimaru Y, Smiljanic K, Sivcev S, Previde RM, Wray S, Balla T, Stojilkovic SS. Postnatal Development and Maintenance of Pituitary Gonadotrophs is Dependent on PI4-kinase A. Endocinology, 2023.
2020-2022
Shan Y, Saadi H, Wray S. Heterogeneous Origin of Gonadotropin Releasing Hormone-1 Neurons in Mouse Embryos Detected by Islet-1/2 Expression. Frontiers in Cell and Developmental Biology, 8:35, 2020.
Saglam A, Calof AC, Wray S. A Novel Factor in Olfactory Ensheathing Cell-Astrocyte Crosstalk: Anti-Inflammatory Protein α-Crystallin B. Glia, 69(4), 2020.
Constantin S, Reynolds, D. Oh, A, Pizano K, Wray S. Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment. PNAS, 118(1), 2021.
Shan, Y. Farmer, SM, Wray, S. Drebrin Regulates Cytoskeleton Dynamics in Migrating Neurons through Interaction with CXCR4. PNAS, 118(3), 2021.
Constantin S, Pizano K, Matson, K, Shan Y, Reynolds D, Wray S. An inhibitory circuit from brainstem to GnRH neurons in male mice: a new role for the RFRP receptor. Endocrinology, 162(5), 2021.
Dairaghi L, Constantin S, Oh A, Shostak D, Wray, S. The Dopamine D4 receptor regulates gonadotropin-releasing hormone neuron excitability in male mice. eNeuro, 2022.
Welch B, Cho H-J, Ucakturk SA, Farmer, SM, Cetinkaya S, Abaci A, Akkus G, Simsek E, Kotan LD, Turan I, Yuksel B, Wray S, Topaloglu AK. PLXNB1 Mutations in the Etiology of Idiopathic Hypogonadotropic Hypogonadism. J. of Neuroendocrinology, 2022.
Pre-2022 (selected)
Wray S, Grant P, Gainer H. Evidence that cells expressing luteinizing hormone releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode. Proc. Natl. Acad. Sci., USA, 86: 8132-8136, 1989.
Kusano K, Fueshko S, Gainer H, Wray S. Electrical and synaptic properties of embryonic LHRH neurons in explant cultures, Proc. Natl. Acad. Sci., USA, 92: 3928-3922, 1995.
Moore JP, Wray S. Luteinizing hormone releasing hormone (LHRH) biosynthesis and secretion in embryonic LHRH neurons, Endocrinology, 141: 4486-4495, 2000.
Kramer PK, Wray S. Novel gene expressed in nasal regions influences outgrowth of olfactory axons and migration of luteinizing hormone releasing hormone (LHRH) neurons, Genes & Development, 14:1824-1834, 2000.
Temple JL, Laing E, Sunder A, Wray S. Direct Action of Estradiol on Gonadotropin-Releasing Hormone-1 Neuronal Activity Via a Transcription–Dependent Mechanism, J. Neuroscience, 24: 6328-6333, 2004.
Constantin S, Caraty A, Wray S, Duittoz A. Development of GnRH-1 secretion in mouse nasal explants, Endocrinology, 150: 3221-7, 2009.
Forni PE, Taylor-Burds C, Melvin S, Williams T, Wray S. Neural Crest and Ectodermal Cells Intermix in the Nasal Placode to give rise to GnRH-1 Neurons, Sensory Neurons and Olfactory Ensheathing Cells, J. Neuroscience 31:6915-27, 2011.
Kotan LD*, Hutchins BI*, Ozkan Y, Demirel F, Stoner H, Cheng PJ, Esen I, Gurbuz F, Y. Bicakci K, Mengen E, Yuksel B, Wray S, Topaloglu AK. Mutations in FEZF1 Cause Kallmann Syndrome. American Journal of Human Genetics, 4;95(3):326-31, 2014.