Post date: 5/10/19
The overall goal of CDNS is to understand how neurons arrive in the correct location, establish appropriate circuitry and a functional unit. We specifically focus on development of the Gonadotropin hormone releasing hormone -1 (GnRH) neuroendocrine system. This system controls reproductive function in all vertebrates. These cells arise in nasal region and migrate into the CNS. These early events rely on proper craniofacial development and expression of guidance cues to direct GnRH cells into the forebrain. Once within the brain, GnRH cells are modulated by numerous systems that effect reproductive function. However, when release of GnRH is pulsatile, the pituitary-gonadal axis is activated, leading to puberty and reproduction. Disruption of development or regulation of the GnRH system results in reproductive dysfunction as is seen in patients with Kallman syndrome. To study the development of the GnRH system requires unraveling cues directing development of the craniofacial region and forebrain. To study the regulation of the GnRH system requires understanding intrinsic properties of GnRH cells and extrinsic cues that alter their function. Thus, using mice for which we have an extensive array of molecular, cellular and genetic tools, our present focus is on 1) the GnRH progenitor and factors which influence establishment of this cell phenotype (neuronal differentiation), 3) molecules, isolated from mouse screens and human genetic studies, which direct GnRH cells to their final destination (neuronal migration), and 3) mechanisms that modulate GnRH neuronal activity. Currently, the lab consists of 1contract scientist, 3 postdoctoral fellows, 1 graduate student, 2 master IRTAs, and 4 postbac IRTAs.
Roles and Responsibilities
Projects focus on differentiation and migration of GnRH cells, olfactory ensheathing cells and olfactory axon outgrowth during development of the craniofacial region. Prenatally, GnRH neurons originate in the nasal region and migrate on olfactory axons into the brain. Current projects examine: 1) lineage of the GnRH cells, 2) intracellular signaling that controls cell movement and corresponding changes in cytoskeletal elements, 3) combinatorial influence of guidance factors involved in migration of these cells into the forebrain; mechanisms common to neuronal migration as well as mechanisms specific to the GnRH system and 4) development of the craniofacial region. Laboratory uses multidisciplinary approaches: cre/lox mice, transgenic lines, imaging, nasal explants, acute slices, videomicroscopy, calcium imaging, electrophysiology, immunocytochemistry, single-cell PCR, CRISPR and subtractive cDNA screening.
About You
Candidate should have training in one of the following: Neurobiology, Development or Neuroendocrinology. Technical training in one of the following is required: confocal microscopy, cell culture, calcium imaging, CRISPR, manipulation of gene expression (siRNA, lentivirus, etc.) and/or in situ hybridization on mouse tissue.
Application
E-mail your interests and long-term goals, a CV and three letters of reference to Dr. S. Wray: wrays@ninds.nih.gov
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