Director, Developmental Biology Alliance
Ph.D. (2002) Massachusetts Institute of Technology
- Member, Anolis Gene Nomenclature Committee
- Grant Support -
- "Developmental Context and the Control of Appendage cis-Regulatory Networks", NIH/NICHD
- "CAREER: Developmental Evolution of Limb Morphology", NSF
- Research Interests -
- How is vertebrate morphology encoded in the genome, and how does vertebrate morphology evolve? Vertebrate limbs are ideal structures in which to study these questions because they are both highly patterned and show remarkable changes in size and form in animals adapted to running, swimming, hopping, digging, or flying. Although many of the genes that control limb growth and patterning have been identified, we know relatively little about how the expression of these genes is regulated and to what degree changes in the regulation of these limb genes has contributed to the evolution of divergent limb morphologies. My lab uses a combination of comparative genomics and functional assays in knockout and transgenic mice to identify key cis-regulatory elements that control the expression of developmentally important limb genes. Current work is focused on the Tbx4 gene, which encodes a T-box transcription factor critical for the formation of the hindlimb. We have demonstrated that hindlimb expression of Tbx4 is controlled by at least two distinct enhancer elements, deletion of one of which reduces expression of Tbx4 in the hindlimb during embryogenesis and produces mice with characteristic decreases in the sizes of bones in the hindlimb. Comparative sequencing of vertebrate species that have evolved partial or complete hindlimb reduction indicates that reduction in the hindlimb size of some species has been accompanied by sequence changes in key hindlimb control regions of Tbx4. Future work will include the use of mouse transgenics and knock-in strategies to test the functional significance of Tbx4 hindlimb control elements during normal mouse development and the biological effects of sequence changes seen in other species.
- Thompson, A.C., Capellini, T.D., Guenther, C.A., Chan, Y.F., Infante, C.R., Menke, D.B., Kingsley, D.M. 2018. A novel enhancer near the Pitx1 gene influences development and evolution of pelvic appendages in vertebrates. eLife. 7. pii: e38555.
- VanLeuven, A.J., Park, S., Menke, D.B., Lauderdale JD. 2018. A PAGE screening approach for identifying CRISPR-Cas9-induced mutations in zebrafish. Biotechniques. 64(6):275-278.
- Tollis, M., Hutchins, E.D., Stapley, J., Rupp, S.M., Eckalbar, W.L., Maayan, I., Lasku, E., Infante, C.R., Dennis, S.R., Robertson, J.A., May, C.M., Crusoe, M.R., Bermingham, E., DeNardo, D.F., Hsieh, S.T., Kulathinal, R.J., McMillan, W.O., Menke, D.B., Pratt, S.C., Rawls, J.A., Sanjur, O., Wilson-Rawls, J., Wilson Sayres, M.A., Fisher, R.E., Kusumi, K. 2018. Comparative Genomics Reveals Accelerated Evolution in Conserved Pathways during the Diversification of Anole Lizards. Genome Biol Evol. 10(2):489-506.
- Wang, J.S., Infante, C.R., Park, S., Menke, D.B. 2018. PITX1 promotes chondrogenesis and myogenesis in mouse hindlimbs through conserved regulatory targets. Dev Biol. 434(1):186-195.
- Ching, S.T., Infante, C.R., Du, W., Sharir, A., Park, S., Menke, D.B., Klein, O.D. 2018. Isl1 mediates mesenchymal expansion in the developing external genitalia via regulation of Bmp4, Fgf10 and Wnt5a. Hum Mol Genet. 27(1):107-119.
- Infante, C.R., Rasys, A.M., Menke, D.B. 2018. Appendages and gene regulatory networks: Lessons from the limbless. Genesis. 56(1). doi: 10.1002/dvg.23078.
- Domyan, E.T, Z. Kronenberg, C. R. Infante, A.I. Vickrey, S.A. Stringham, R. Bruders, M.W. Guernsey, S. Park, J. Payne, R.B. Beckstead, G. Kardon, D.B. Menke, M. Yandell, M.D. Shapiro. 2016. Molecular shifts in limb identity underlie development of feathered feet in two domestic avian species. eLife. 5: e12115.
- Infante, C.R., A.G. Mihala, S. Park, J.S. Wang, K.K. Johnson, J.D. Lauderdale, and D.B. Menke. 2015. Shared enhancer activity in the limbs and phallus and functional divergence of a limb-genital cis-regulatory element in snakes. Dev Cell. 35(1):107-19.
- Kumar, M.E., P.E.Bogard, F.H. Espinoza, D.B. Menke, D.M. Kingsley, and M.A. Krasnow. 2014. Defining a mesenchymal progenitor niche at single-cell resolution. Science. 346(6211): 1258810.
- Park, S., C.R. Infante, L.C. Rivera-Davila and D.B. Menke. 2014. Conserved regulation of hoxc11 by pitx1 in Anolis lizards. Journal of Experimental Zoology B. 322: 156-165.
- D.B. Menke. 2013. Engineering subtle targeted mutations into the mouse genome. Genesis. 51: 605-618.
- Infante, C.R., S. Park, A. Mihala, D.M. Kingsley and D.B. Menke. 2013. Pitx1 Broadly Associates with Limb Enhancers and is Enriched on Hindlimb cis-Regulatory Elements. Developmental Biology. 374: 234-244.
- Kusumi, K., R.J. Kulanthinal, A. Abzhanov, S. Boissinot, N.G. Crawford, B.C. Faircloth, T.C. Glenn, D.E. Janes, J.B. Losos, D.B. Menke, S. Poe, T.J. Sanger, C.J. Schneider, J. Stapley, J. Wade and J. Wilson-Rawls. 2011. Developing a community-based genetic nomenclature for anole lizards. BMC Genomics. 12: 554.
- McLean, C.Y., P.L. Reno, A.A. Pollen, A.I. Bassan, T.D. Capellini, C. Guenther, V.B. Indjeian, X. Lim, D.B. Menke, B.T. Schaar, A.M. Wenger, G. Bejerano and D.M. Kingsley. Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature. 471: 216-219.
- Menke, D.B., C. Guenther and D.M. Kingsley. 2008. Dual hindlimb control elements in the Tbx4 gene and region-specific control of bone size in vertebrate limbs. Development. 135: 2543-2553.