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Mammalian Development Section
Heinz Arnheiter, M.D., Senior Investigator
Dr. Arnheiter received his M.D. degree from the University of Zurich, Switzerland. His initial work at its Institute for Virology focused on the family of Mx proteins which are intrinsic host factors serving as the first lines of defense against infections with influenza viruses. He joined the former Laboratory of Molecular Genetics at NINDS to work on intracellular protein trafficking and viral assembly. After a brief time in Zurich, he returned to the NINDS and in 1986 introduced transgenic technology to the institute. He later shifted from studies of host defense mechanisms to the development of the nervous system. His group is now focusing on molecular mechanisms of neural crest development and patterning of the neuroepithelium in the eye and neural tube.
Staff:
- Stefano Bertuzzi, Ph.D., Staff Scientist, 301-496-9661 bertuzzs@mail.nih.gov
- Kapil Bharti, Ph.D., Postdoctoral Fellow, 301-496-9661 kapilbharti@ninds.nih.gov
- Julien Debbache, B.S., Graduate Student, 301-496-9661 debbachej@ninds.nih.gov
- Melanie Gasper, B.S., Post baccalaureate Fellow, 301-496-9661 gasperm@ninds.nih.gov
- Susan Skuntz, M.Sc, Research Assistant, 301-496-9661 skuntzs@ninds.nih.gov
- Xin Wang, Ph.D., Postdoctoral Fellow, 301-496-9661 wangxin2@mail.nih.gov
Research Interests:
A detailed knowledge of the molecular mechanisms that govern the generation of distinct cell types from unspecified precursors will not only help us understand fundamental principles of normal ontogeny but also explain, and ultimately correct, instances where development has derailed and disease has resulted. We are currently focusing on the developmental role of the basic-helix-loop-helix-zipper transcription factor MITF and its integration with signaling pathways. Mutations in this factor are found from fish to man and in mammals are associated with pigment disturbances, eye abnormalities, and hearing deficiencies (Waardenburg syndrome type II). Recent results indicate that MITF is under stringent transcriptional and post-transcriptional control by extrinsic growth factors such as FGF or KIT-ligand, and that it is the interplay between these extrinsic factors and MITF that result in cell lineage determination. We focus on the development of two organ systems, the eye where the bipotential optic neuroepithelium segregates into retina and retinal pigment epithelium, and the neural crest where multipotential precursor cells give rise to MITF-positive melanoblasts and MITF-negative neuronal and glial cells of the peripheral nervous system. To delineate molecular hierarchies in the relevant pathways, we study a large series of MITF mutant mice and use genetic tools including the generation of transgenic and targeted knock-in mice. The ultimate goal of these studies is to characterize the network of factors involved in the generation and function of derivatives of the neuroepithelium and the neural crest that are crucial for the development and function of mammalian sensory organs.
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Selected Publications:
- Heinz Arnheiter and Kapil Bharti (2008) Ribosomes and p53 - a new KIT for skin darkening, Pigment Cell and Melanoma Research . Full Text/Abstract
- Bharti, K, Liu, W, Csermely, T, Bertuzzi, S, Arnheiter, H. (2008) Alternative promoter use in eye development: the complex role and regulation of the transcription factor MITF, Development 135, 1169-1178. Full Text/Abstract
- Bismuth, K., Skuntz, S., Hallsson, J.H., Pak, P., Dutra, A.B., Steingrimsson, E., Arnheiter, H. (2008) An unstable targeted allele of the mouse Mitf gene with a high somatic and germ line reversion rate, Genetics 178, 259-272. Full Text/Abstract
- Arnheiter, H. (2007) Mammalian paramutation: a tail's tale?, Pig Cell Res 20, 36-40. Full Text/Abstract
- Hallsson, JH, Haflidadottir, BS, Schepsky, A, Arnheiter, H, Steingrimsson, E (2007) Evolutionary sequence comparison of the Mitf gene reveals novel conserved domains, Pigment Cell Research 20, 185-200. Full Text/Abstract
- Hou, L., Arnheiter, H. and Pavan, W.J. (2006) Interspecies difference in the regulation of melanocyte development by SOX10 and MITF, Proc. Natl. Acad. Sci. (USA) 103, 9081-9085. Full Text/Abstract
- Bharti, K., Nguyen, M.-T. T., Skuntz, S., Nakayama, A., Bertuzzi, S., and Arnheiter, H. (2006) The other pigment cell: Specification and development of the pigmented epithelium of the vertebrate eye, Pigment Cell Research 19, 380-394. Full Text/Abstract
All Selected Publications
Contact Information:
Dr. Heinz Arnheiter
Laboratory of Developmental Neurogenetics, NINDS
Porter Neuroscience Research Center
Building 35, Room 2A-201
35 Convent Drive, MSC 3706
Bethesda, MD 20892-3706
Telephone: 301-496-1645 office,
301-496-9661 laboratory,
301-480-2737 fax
Email: ha3p@nih.gov
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