Christopher B. Geyer, Ph.D.

Christopher B. Geyer, Ph.D.

Assistant Professor

B.S., Virginia Polytechnic Institute and State University
Ph.D., The University of Texas Health Science Center at San Antonio
Postdoctoral Fellow, National Institute of Environmental Health Sciences

office: 7N-84
telephone: 252-744-3433
e-mail: geyerc@ecu.edu

| Research | Selected Publications | Staff and Students |

Research
My laboratory uses mouse spermatogenesis as a model system to investigate mechanisms involved in regulating cellular differentiation. Research in the field of spermatogenesis has relied heavily on the use of genetically modified mice to increase understanding of the processes necessary for normal germ cell development. The study of these models will increase our understanding of the processes necessary for normal fertility and have the potential for guiding the production of new reagents useful for diagnosing causes of human male factor infertility.

Male gametes develop within the seminiferous epithelium in intimate contact with somatic Sertoli cells under the influence of a combination of paracrine and endocrine signals. Sertoli cells cease dividing and terminally differentiate at puberty (~P15 in the mouse), and physically span the seminiferous epithelium in preparation for their eventual support of every phase of germ cell development (at male sexual maturity, ~P40-50). At the basal aspect of the tubule, they provide the stem cell niche for spermatogonia that asynchronously divide to give rise to spermatocytes that will enter meiosis. Spermatogonia must cross the blood-testis barrier, a tight junction between adjacent Sertoli cells that functionally separates the basal from the adluminal compartments. They then enter meiosis as spermatocytes, going through successive divisions to produce haploid spermatids. Following meiosis, these spermatids undergo spermiogenesis, a series of complex morphological changes that will result in the highly specialized spermatozoon. The successful completion of each of these processes outlined above requires the expression of unique sets and combinations of genes.

We are currently working on two main projects designed to investigate cellular differentiation during spermatogenesis:

Study 1: The novel nuclear role of the palladin gene (Palld) product in Sertoli cell differentiation. In the majority of cell types in the body, PALLD functions as a cytoplasmic actin regulatory protein. In Sertoli cells of the testis, however, PALLD is localized within nuclei starting at postnatal (P) day 15, at which point Sertoli cells stop dividing and differentiate to serve as a “nurse cell” to support all aspects of male germ cell development. My working hypothesis, based on a proposed role for nuclear actin, is that PALLD stabilizes transcription factor complexes and therefore regulates the expression of genes essential for Sertoli function. However, much work needs to be done to test this hypothesis. Initially, we will generate mice with a selective deletion of the Palld gene in Sertoli cells and characterize their reproductive potential. Future experiments will be aimed at understanding how the expression of the nuclear Palld isoform is regulated, to identify PALLD binding partners, and to define the relationship between PALLD expression and cessation of Sertoli cell division.

Study 2: The role of the reproductive homeobox gene 13 (Rhox13) product in differentiating germ cells in the mouse. The active form of vitamin A, retinoic acid (RA), provides an exogenous signal for both male and female germ cells to differentiate and ultimately enter meiosis. Although many cell types are exposed to RA, only germ cells respond by initiating meiosis. I am interested in how this signal directs the expression (or repression) of germ-cell specific factors and pathways that lead to differentiation and meiotic initiation. To address this, I am investigating a novel germ cell-expressed homeobox gene that I discovered during my postdoctoral fellowship, Rhox13, whose transcripts are only translated in differentiating germ cells of the murine ovary and testis at the time when RA signaling is initiated. Rhox13 transcripts and protein are both detectable as early as embryonic day (E)13.5 in oogonia in the fetal ovary. In the testis, however, transcripts are not translated until postnatal day P4. Two pieces of preliminary data implicate RA in this translational delay: 1) RA induces translation of Rhox13 in neonatal testis explants in culture, and 2) RHOX13 protein is aberrantly expressed in embryonic gonocytes of mice lacking NANOS2, an RA-responsive RNA binding protein that is required for maintenance of germline stem cells. I am generating both male and female Rhox13 knockout mice, which will allow me to examine the function of RHOX13 in germ cell differentiation and meiotic investigation. I have successfully targeted the Rhox13 gene in two different ES cell lines, and am currently collaborating with the Eddy laboratory at the NIEHS to produce these mice.

Selected Publications
Keiser, J.T., P.M. Jobst, A.S. Garst, J.T. Boone, C.B. Geyer, C. Phelps, D.L. Ayares, and R.L. Page. 2001. Preimplantation screening for transgenesis using an embryonic specific promoter and green fluorescent protein. Cloning 3: 23-30.

Geyer, C.B., C.M. Kiefer, T. Yang, and J.R. McCarrey. 2004. Ontogeny of a demethylation domain and its relationship to activation of tissue-specific transcription. Biol. Reprod. 71: 837-844.

McCarrey, J.R., C.B. Geyer, and H. Yoshioka. 2005. Epigenetic regulation of testis-specific gene expression. Ann. N.Y. Acad. Sci. 1061: 226-242.

Yoshioka, H., C.B. Geyer, J.L. Hornecker, K.T. Patel, and J.R. McCarrey. 2007. In vivo analysis of developmentally and evolutionarily dynamic protein-DNA interactions regulating transcription of the Pgk2 gene during mammalian spermatogenesis. Mol. Cell Biol. 27: 7871-7885.

Geyer, C.B. and E.M. Eddy. 2008. Identification and characterization of Rhox13, a novel X-linked mouse homeobox gene. Gene 423: 194-200.

Geyer, C.B., A.I. Inselman, J. Sunman, S. Bornstein, M.A. Handel, and E.M. Eddy. 2009. A missense mutation in the Capza3 gene and disruption of F-actin organization in spermatids of repro32 infertile male mice. Dev. Biol. 330: 142-152.

Danshina, P.V., C.B. Geyer, Q. Dai, E.H. Goulding, W.D. Willi, G.B. Kitto, J.R. McCarrey, E.M. Eddy, and D.A. O’Brien. 2009. Phosphoglycerate kinase 2 (PGK2) is essential for sperm function and male fertility in mice. Biol. Reprod. 82: 136-145

Staff and Students
Location 7N-59

Name	Title	Phone	E-mail
Bryan Niedenberger	Research Technician	744-2833	niedenbergerb@ecu.edu