Research focus of 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: 1) signals for proper craniofacial development, 2) guidance factors that modulate neuronal migration and 3) 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.
- Forni PE, Taylor-Burds C, Melvin VS, 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 Neurosci. 2011;31(18):6915-27.
- Hutchins BI, Kotan LD, Taylor-Burds C, Ozkan Y, Cheng PJ, Gurbuz F, Tiong JD, Mengen E, Yuksel B, Topaloglu AK, Wray S. CCDC141 Mutation Identified in Anosmic Hypogonadotropic Hypogonadism (Kallmann Syndrome) Alters GnRH Neuronal Migration. Endocrinology. 2016;157(5):1956-66.
- Shan Y, Farmer SM, Wray S. Drebrin regulates cytoskeleton dynamics in migrating neurons through interaction with CXCR4. Proc Natl Acad Sci U S A. 2021;118(3).
- Constantin S, Reynolds D, Oh A, Pizano K, Wray S. Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment. Proc Natl Acad Sci U S A. 2021;118(1).
- Shostak DM, Constantin S, Flannery J, Wray S. Acetylcholine regulation of GnRH neuronal activity: A circuit in the medial septum. Front Endocrinol (Lausanne). 2023;14:1147554.
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This page was last updated on Monday, August 14, 2023