Richard R. Behringer, Ph.D. 1986, University of South Carolina UT M. D. Anderson Cancer Center Genetics Contact Information Biographical Sketch

Research Interests: Mammalian embryogenesis; reproductive biology and disease; stem cell biology; evolution and development

Our research focuses on the molecular and cellular mechanisms that lead to the formation of the mammalian body plan, the genesis of tissues and organs during embryogenesis, and the pathology of developmental defects. In addition, we study the genetic mechanisms that result in organ morphology and physiology differences that have evolved between species. We utilize genetic, embryological, and comparative approaches.

The mammalian reproductive organs are essential for the continuation of species and are common sites for disease. We are interested in defining the factors that cause the male and female phenotypes, including gonad and reproductive tract differentiation. To facilitate these studies, we have generated transgenic mice expressing novel fluorescent reporters for live-imaging to follow the behaviors of cells during reproductive organ formation. In addition, we are creating mouse models for cancers of the reproductive organs, e.g. the ovary. These mouse models may be useful for understanding the formation of human ovarian cancer and devising therapies.

Stem cells can generate more of themselves (self-renewal) or can produce the different cell types of the body (differentiation). Embryonic stem (ES) cells are derived from pre-implantation embryos and have the potential to form any cell type of the body. Adult stem cells are present in our bodies to replenish cells that wear out (for example red blood cells, skin, and even neurons). Adult stem cells can give rise to single or multiple cell types. We are currently genetically modifying human ES cells and other types of stem cells to devise future therapies of human disease.

We are also investigating developmental processes in divergent mammalian systems, including marsupials and chiropterans (bats). Mammalian embryogenesis and reproduction are very diverse between species, comparisons provide novel insights for reproduction, embryonic development, and organogenesis. We collaborate with Marilyn Renfree (U. Melbourne) using the tammar wallaby (Macropus eugenii) model to study sexual differentiation and limb development. Bats also offer a unique system to study the genetic mechanisms that diversify organogenesis. We have collaborated with John Rasweiler (SUNY Downstate) to establish the molecular embryology of the fruit bat, Carollia perspicillata, and are transferring bat genes into mice for functional studies of limb development. Our wallaby and bats studies are supported by field collections on Kangaroo Island, Australia and the island of Trinidad, respectively.

Rats are large laboratory rodents that are useful for studies of physiology, behavior, and other fields of biology. The rat genome has been sequenced, assembled, and annotated. One particularly valuable resource to facilitate studies of mammalian gene function that is sorely lacking in the rat system is a large collection of mutants and a continuous source of new mutations. The ability to easily generate new mutant rat strains and to efficiently identify the mutated genes would significantly advance the use of this primary laboratory animal for biomedical research. We have used coat color-tagged transposons (piggyBac and Sleeping Beauty) to generate transgenic rats for random insertional mutagenesis. Our mutagenesis screen should lead to new rat models of human biology and disease.
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Cretekos, C.J., Wang, Y., Green, E.D., NISC Comparative Sequencing Program, Martin, J.F., Rasweiler, J.J. IV, and Behringer, R.R. (2008) Regulatory divergence modifies forelimb length in mammals. Genes Dev. 22: 141-51.

Zhao, Y., Kwan, K.M., Mailloux, C.M., Lee, W.-K., Grinberg., A., Wurst, W., Behringer, R.R., and Westphal, H. (2007) LIM-homeodomain proteins Lhx1, Lhx5 and their cofactor Ldb1 control Purkinje cell differentiation in the developing cerebellum. Proc. Natl. Acad. Sci. U.S.A. 104, 13182-6.

Orvis, G.D. and Behringer, R.R. (2007) Cellular mechanisms of Müllerian duct formation in the mouse. Dev. Biol. 306, 493-504.  

Cretekos, C.J., Weatherbee, S.D., Chen, C.-H., Badwaik, N.K., Niswander, L., Behringer, R.R. , and Rasweiler, J.J., IV (2005) Embryonic staging system for the short-tailed fruit bat, Carollia perspicillata , a model organism for the mammalian order Chiroptera , based upon timed pregnancies in captive-bred animals. Dev. Dyn. , 233(3) :721-38.

Kobayashi, A., Kwan, K.M., Carroll, T.J, McMahon, A.P., Mendelsohn, C.L., and Behringer, R.R. (2005) Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development 132(12) :2809-23.

Pask, A.J., Kanasaki, H., Kaiser, U.B., Stockton, D.W., Hess, D.L., Justice, M.J., and Behringer, R.R. (2005) A novel mouse model of hypogonadotrophic hypogonadism : ENU-induced gonadotrophin releasing hormone receptor gene mutation.  Mol. Endocrinol ., 19(4) :972-81.

Chaboissier M, Kobayashi A, Vidal VI, Lützkendorf S, van de Kant HJ, Wegner M, de Rooij DG, Behringer RR , Schedl A. (2004) Functional analysis of Sox8 and Sox9 during sex determination in the mouse. Development 131 , 1891–1901.

Chen C-M, Behringer RR . (2004) Ovca1 regulates cell proliferation, embryonic development, and tumorigenesis. Genes Dev. 18 , 320–332.

Kobayashi A, Shawlot W, Kania A, Behringer RR . (2003) Requirement of Lim1 for female reproducive tract development. Development 131 , 539–549.

Jamin SP, Arango NA, Mishina Y, Hanks MC, Behringer RR . (2002) Requirement of BMPR-IA for Müllerian duct regression during male sexual development. Nature Genetics 32 , 408–410.

Arango NA, Lovell-Badge R, Behringer RR (1999) Targeted mutagenesis of the endogenous Müllerian inhibiting substance gene promoter: In vivo definition of genetic pathways of vertebrate sexual development. Cell 99 , 409–419.

Liu, P., Wakamiya, M., Shea, M.J., Behringer, R.R. , and Bradley, A. (1999) Wnt3 is essential for gastrulation in the mouse.  Nature Genetics 22 , 361–365.

Li, Y. and Behringer R.R. (1998) Esx1 is an X-chromosome-imprinted regulator of placental development and fetal growth. Nature Genetics 20 , 309–311.

Mishina, Y., Rey, R., Finegold, M.J., Matzuk, M.M., Josso, N., Cate, R.L., and Behringer, R.R. (1996) Genetic analysis of the Müllerian-inhibiting substance signal transduction pathway in mammalian sexual differentiation.  Genes Devel . 10 :2577–2587.

Mishina Y, Suzuki A, Ueno N, Behringer RR (1995) Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes Dev. 9 , 3027–3037.

Horan, G.S.B., Ramirez-Solis, Ramiro, Featherstone, M.S., Wolgemuth, D.J., Bradley, A. and Behringer, R. R. (1995) Compound mutants for the paralogous hoxa-4 , hoxb-4 , and hoxd-4 genes show more complete homeotic transformations and a dose-dependent increase in the number of vertebrae transformed. Genes Devel. 9 :1667–1677.

Chen, Z.-F. and Behringer, R.R. (1995) twist is required in head mesenchyme for cranial neural tube morphogenesis.  Genes Devel. 9 :686–699.

Shawlot W, Behringer RR (1995) Requirement for Lim1 in head-organizer function. Nature 374 , 425–430.

Behringer R.R., Finegold, M.J., and Cate, R.L. (1994) Müllerian inhibiting substance function during mammalian sexual development. Cell 79 :415–425.