Dr. Nathans and his laboratory are interested in the mammalian visual system and, in particular, the retina, the light-absorbing sheet of cells that lines the back of the eye. Their general approach is to use the tools of molecular genetics to identify and study genes involved in development, function, and disease. A second interest is in elucidating the mechanisms of pattern formation during animal development and, in particular, the role of the Frizzled family of cell-surface receptors. These two interests have converged with our discovery of a Frizzled-based system for controlling the development and integrity of retinal blood vessels.
Currently, they are working on defining the roles of Frizzled receptors in mammalian development. The foundation of our approach is the production and analysis of mice carrying targeted null or conditional null mutations in one or more Frizzled genes. They have constructed such lines for each of the ten Frizzleds, as well as for other genes that act in the same signaling pathways. This genetic analysis has revealed both diversity and unity in the functions of different Frizzled receptors, and has revealed the requirement for Frizzled signaling in a wide variety of developmental contexts, including axon guidance, vascular growth and differentiation, inner ear development, neural tube and palate closure, kidney development, and hair orientation on the body surface.
The Nathans laboratory is focused on several broad and related areas of research: (1) neural and vascular development, and (2) the role of Frizzled receptors in mammalian development. They use gene manipulation in the mouse, cell culture models, and biochemical reconstitution to investigate the relevant molecular events underlying these processes, and to genetically mark and manipulate cells and tissues.
Lab Website: Jeremy Nathans Laboratory
Yu, H., Ye, X., Guo, N. and Nathans, J. "Frizzled2 and Frizzled7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes." Development 139: 4383-4394. (2012)
Wang, Y., Rattner, A., Zhou, Y., Williams, J., Smallwood, P.M., and Nathans, J. "Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity." Cell 151: 1332-1344. (2012)
Wu, H., Williams, J., and Nathans, J. "Morphologic diversity of cutaneous sensory afferents revealed by genetically directed sparse labeling." eLife 1:e00181. (2012)
Badea, T.C., Williams, J., Smallwood, P., Shi, M., Motajo, O., and Nathans, J. "Combinatorial expression of Brn3 transcription factors in somatosensory neurons: genetic and morphologic analysis." Journal of Neuroscience. 32: 995-1007. (2012)
Ye, X., Wang, Y., Rattner, A., and Nathans, J. "Genetic mosaic analysis reveals a major role for frizzled4 and frizzled8 in controlling ureteric growth in the developing kidney." Development 138: 11161-1172. (2011)