Paul A. Overbeek, Ph.D.
Department of Molecular and Cellular Biology
Ph.D.: University of Michigan, Ann Arbor
Postdoctoral training: National Institutes of Health, Bethesda
Mouse Models for Human Birth Defects
My laboratory is interested in defining the molecular pathways that regulate cell fate determination. Two different strategies are used. Both strategies make use of transgenic mice. In the first strategy, differentiation decisions are studied and altered in a model organ, the eye. In the second system, random insertional mutations are used to identify novel genes that are required for normal embryogenesis.
Within the eye, developmental decisions in the cornea, lens, and retina are all influenced by environmental signals. My laboratory has identified and characterized promoters that can be used to target transgene expression to these different regions of the eye during embryonic development. These promoters have been used to express extracellular signaling proteins, such as growth factors, in the eye. Using this strategy, we have discovered that fibroblast growth factors (FGFs) can specify alternative developmental fates for the different epithelial cells of the eye. We are now working to identify the signal transduction proteins, transcription factors, and genes that are activated and/or inhibited in vivo in response to specific FGFs.
In addition to research on eye development, we generate and characterize mouse models for human birth defects. To date we have identified mutations that affect left-right asymmetry, sex determination, hair follicle induction, CNS morphogenesis, craniofacial and inner ear development, skin maturation, growth, fertility, and digit identity. We have cloned and are characterizing genes required for kidney and hair follicle induction. Current research is focused on identifying the molecular mechanisms by which these genes regulate morphogenesis during embryogenesis.
Expression of downless, a novel TNF receptor homolog, in fetal mouse skin. Downless is required for induction of hair follicles.
Baylor College of Medicine
One Baylor Plaza, Alkek N620.03
Houston, TX 77030
- Lu B, Geurts AM, Poirier C, Petit DC, Harrison W, Overbeek PA and Bishop CE. (2007). Generation of rat mutants using a coat color-tagged Sleeping Beauty transposon system. Mamm. Genome 18:338-346.
- Xie L, Chen H, Overbeek PA and Reneker LW. (2007). Elevated insulin signaling disrupts the growth and differentiation pattern of the mouse lens. Mol Vis. 13:397-407.
- Xie L, Overbeek PA and Reneker LW. (2006). Ras-signaling is essential for lens cell proliferation and lens growth during development. Dev Biol. 298:403-414.
- Mou C, Jackson B, Schneider P, Overbeek PA and Headon DJ. (2006). Generation of the primary hair follicle pattern. Proc. Natl. Acad. Sci. USA 103:9075-9080.
- Govindarajan V and Overbeek PA. (2006). FGF9 can induce endochondral ossification in cranial mesenchyme. BMC Dev. Biol. 6:7-14.
- Govindarajan V, Harrison WR, Xiao N, Liang D and Overbeek PA. (2005). Intracorneal positioning of the lens In Pax6-Gal4/VP16 transgenic mice. Mol. Vis. 11:876-886.
- Yang T, Liang D, Koch PJ, Hohl D, Kheradmand F and Overbeek, P.A. (2004). Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- mice. Genes Dev. 18:2354-2358.
- Chen Q, Liang D, Yang T, Leone G and Overbeek PA. (2004). Distinct capacities of individual E2Fs to induce cell cycle re-entry in postmitotic lens fiber cells of transgenic mice. Dev. Neurosci. 26:435-445.
- Chen Q, Liang D, Fromm LD and Overbeek PA. (2004). Inhibition of lens fiber cell morphogenesis by expression of a mutant SV40 large T antigen that binds CBP/p300 but not pRb. J. Biol. Chem. 279:17667-17673.
- Headon DJ, Emmal SA, Ferguson BM, Tucker AS, Justice MJ, Sharpe PT, Zonana J and Overbeek PA. (2001). Gene defect in ectodermal dysplasia implicates a death domain adapter in development. Nature 414: 913–916.