Kevin Jones

Molecular, Cellular & Developmental Biology; Member of the Center for Neuroscience

Department of Molecular, Cellular & Developmental Biology, Campus Box 347
MCDB Addition Room A445
University of Colorado at Boulder
Boulder, CO 80309-0347

email: krjones@stripe.Colorado.EDU
Phone: 303-492-1363
FAX: 303-492-7744
Website: http://mcdb.colorado.edu/faculty/jones99.html

The nervous system is formed by a regulated sequence of events:
1.controlled proliferation of neuronal precursors
2.specification of fates for the precursors
3.process outgrowth, cell death
4.terminal differentiation of the remaining cells

The resulting network of cells is capable of modifying its behavior based upon stimuli from the outside world, thereby altering the behavior of the organism. What are the molecular mechanisms that underlie the development, function, and deterioration in disease of this extraordinary cellular network? It is now clear that cell interactions have a critical role in both the development and function of the nervous system. What molecules convey these signals? A family of polypeptide hormones, the neurotrophins, are members of the nerve growth factor [NGF] family) are of particular interest because of their striking activities on cultured neurons, supporting their survival and process outgrowth. This family includes the prototypical neurotrophin NGF as well as brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5.

Powerful techniques have been developed for the generation of mice having genetic modifications created in vitro ("knock-out mice") in embryonic stem cells. Dr. Jones˙ laboratory uses these techniques to study gene function in the development of the mammalian nervous system. He now knows, from the study of mouse mutants, that neurotrophins are absolutely required for the survival and development of specific neuronal cell types. The study of null mutations in mice has limitations, particularly when the mutation results in lethality at an early stage of the life cycle. One very exciting approach Dr. Jones has pursued to circumvent these problems is to create mice that have a mutation only in a specific tissue (genetic mosaics) through the use of the cre/lox recombinase system. This approach will be quite valuable in dissecting gene functions in a specific tissue or at a specific developmental stage where null mutations would be uninformative or lethal. Initially, Dr. Jones has focused on the neurotrophin BDNF, studying its functions in the brain and peripheral nervous system. In the course of this work, he has developed valuable strains of mice that he will also use in the analysis of other genes relevant to neural development through the generation of tissue-specific mutants.

Selected Publications:

Bennett, J. L. S.R. Zeiler and K.R. Jones. (1999) Patterned Expression of BDNF and NT-3 in the Retina and Anterior Segment of the Developing Mammalian Eye. Investigative Ophthalmology and Visual Science. 40:2996-3005.

Vigers, A.J., Z.C. Baquet and K.R. Jones. (2000) Expression of neurotrophin-3 in the mouse telencephalon: Insights from a Targeted lacZ Reporter. J. Comp. Neurol. 416:398-415.

Gorski, J.A., Talley, T., Qiu, M., Puelles, L., Rubenstein, J.L.R., and K.R.
Jones (2002) Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J. Neuroscience 22(15): 6309-14.

Gorski, J.A., Zeiler, S.R., Tamowski, S., and K.R. Jones (2003) BDNF is required for the maintenance of cortical dendrites. J. Neuroscience 23(17):6856-65

Gorski, J.A., Balogh, S.A., Wehner, J.M., and K.R. Jones (200X) Learning deficits in forebrain-restricted BDNF mutant mice. Neuroscience In press