Regulatory divergence modifies limb length between mammals
Open accessAbstract
Natural selection acts on variation within populations, resulting in modified organ morphology, physiology, and ultimately the formation of new species. Although variation in orthologous proteins can contribute to these modifications, differences in DNA sequences regulating gene expression may be a primary source of variation. We replaced a limb-specific transcriptional enhancer of the mouse Prx1 locus with the orthologous sequence from a bat. Prx1 expression directed by the bat enhancer results in elevated transcript levels in developing forelimb bones and forelimbs that are significantly longer than controls because of endochondral bone formation alterations. Surprisingly, deletion of the mouse Prx1 limb enhancer results in normal forelimb length and Prx1 expression, revealing regulatory redundancy. These findings suggest that mutations accumulating in pre-existing noncoding regulatory sequences within a population are a source of variation for the evolution of morphological differences between species and that cis -regulatory redundancy may facilitate accumulation of such mutations.
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Several cases of dramatic morphological changes that occurred very recently are due to alteration in regulation of single genes encoding signaling ligands or transcription factors.
“There are now several justly famous cases where dramatic morphological changes that have occurred very recently have been shown to be due to alteration in regulation of single genes, encoding either signaling ligands (Abzhanov et al. 2006) or transcription factors (Cretekos et al. 2008; Chan et al. 2009; Rebeiz et al. 2009).”
From An integrated view of precambrian eumetazoan evolution (2009) · cites this paper as Cretekos et al. 2008
The Abstract and Results report that replacing a mouse Prx1 enhancer with its bat counterpart increased Prx1 expression and lengthened mouse forelimbs, supporting an effect of altered regulation of a transcription-factor gene. But the Results describe a 6% length increase, and the Discussion calls this a possible slight modification toward bat-wing evolution—not proof that a dramatic, recent natural change was caused by regulation of a single gene. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredInserting the bat prx1 limb enhancer into the mouse gene caused recipient mouse forelimbs to develop with relatively longer dimensions.
“The (indirect) causality of this change was then demonstrated by inserting the bat prx1 limb enhancer into the mouse gene, with the result that the forelimbs of the recipient mouse now develop with relatively longer dimensions.”
From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Cretekos et al., 2008
The longer relative forearm skeleton length in bats compared to rodents is associated with up-regulation of prx1 after early limb bud stage.
“A candidate regulatory gene known to affect limb skeletal elongation is prx1 (mhox), and in bats this gene is up-regulated after the early limb bud stage compared to mice (Cretekos et al., 2008).”
From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Cretekos et al., 2008
Variation in gene expression mediated by cis-regulatory elements plays an important role in evolutionary phenotypic change.
“Variation in gene expression mediated by cis-REs plays an important role in evolutionary phenotypic change (32, 42–46).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [45]
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Cites
Darwin, C. R., Darwin, C. R., & Edmonds & Remnants (1859) · J. Murray eBooks · doi:10.5962/bhl.title.59991 · Cited by 7,019 · see citing works
Cellular Scaling Rules for the Brains of Marsupials: Not as “Primitive” as Expected
Santos, S. E. D., Porfírio, J., Cunha, F., Manger, P. R., Tavares, W. C., Pessôa, L. M., Raghanti, M. A., Sherwood, C. C., & Herculano‐Houzel, S. (2017) · Brain Behavior and Evolution · doi:10.1159/000452856 · Cited by 2,651 · see citing works
Manipulating the Mouse Embryo: A Laboratory Manual
Behringer, R. R., Gertsenstein, M., Nagy, K. V., & Nagy, A. (2002) · Cited by 2,046 · see citing works
Self-citationMansour, S. L., Thomas, K. R., & Capecchi, M. R. (1988) · Nature · doi:10.1038/336348a0 · Cited by 1,683 · see citing works
In situ hybridization; a practical approach
(1993) · International Journal of Biochemistry · doi:10.1016/0020-711x(93)90093-t · Cited by 1,240 · see citing works
Darwin, C. R. (1860) · The Crayon · doi:10.2307/25528056 · Cited by 1,168 · see citing works
A Molecular Phylogeny for Bats Illuminates Biogeography and the Fossil Record
Teeling, E. C., Springer, M. S., Madsen, O., Bates, P. J. J., O’Brien, S. J., & Murphy, W. J. (2005) · Science · doi:10.1126/science.1105113 · Cited by 1,142 · see citing works
Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs.
Brinster, R. L., Chen, H. Y., Trumbauer, M. E., Yagle, M. K., & Palmiter, R. D. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.13.4438 · Cited by 1,028 · see citing works
From DNA to diversity: molecular genetics and the evolution of animal design
Carroll, S., Grenier, J., & Weatherbee, S. D. (2002) · Choice Reviews Online · doi:10.5860/choice.39-5182 · Cited by 986 · see citing works
Ornitz, D. M., & Marie, P. J. (2002) · Genes & Development · doi:10.1101/gad.990702 · Cited by 902 · see citing works
Evolution at Two Levels: On Genes and Form
Carroll, S. B. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030245 · Cited by 882 · see citing works
Genetic and developmental basis of evolutionary pelvic reduction in threespine sticklebacks
Shapiro, M. D., Marks, M. E., Peichel, C. L., Blackman, B. K., Nereng, K. S., Jónsson, B., Schluter, D., & Kingsley, D. M. (2004) · Nature · doi:10.1038/nature02415 · Cited by 843 · see citing works
Müllerian-inhibiting substance function during mammalian sexual development.
Behringer, R., Finegold, M., & Cate, R. (1994) · Cell · doi:10.1016/0092-8674(94)90251-8 · Cited by 706 · see citing works
Self-citationChance caught on the wing: cis-regulatory evolution and the origin of pigment patterns in Drosophila
Gompel, N., Prud'homme, B., Wittkopp, P. J., Kassner, V. A., & Carroll, S. B. (2005) · Nature · doi:10.1038/nature03235 · Cited by 646 · see citing works
Theiler, K. (1989) · Springer eBooks · doi:10.1007/978-3-642-88418-4 · Cited by 601 · see citing works
Repeated morphological evolution through cis-regulatory changes in a pleiotropic gene
Prud'homme, B., Gompel, N., Rokas, A., Kassner, V. A., Williams, T. M., Yeh, S.-D., True, J. R., & Carroll, S. B. (2006) · Nature · doi:10.1038/nature04597 · Cited by 507 · see citing works
PERSPECTIVE: EVOLUTIONARY DEVELOPMENTAL BIOLOGY AND THE PROBLEM OF VARIATION
Stern, D. L. (2000) · Evolution · doi:10.1111/j.0014-3820.2000.tb00544.x · Cited by 483 · see citing works
O’Gorman, S., Dagenais, N., Qian, M., & Marchuk, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14602 · Cited by 436 · see citing works
Laubichler, M. D. (2003) · Max Planck Institute for Plasma Physics · Cited by 387 · see citing works
From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design (review)
Laubichler, M. D. (2003) · Perspectives in biology and medicine · doi:10.1353/pbm.2003.0012 · Cited by 387 · see citing works
Long-range disruption of gene expression by a selectable marker cassette
Pham, C. T. N., MacIvor, D. M., Hug, B. A., Heusel, J. W., & Ley, T. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.13090 · Cited by 365 · see citing works
Martin, J. F., Bradley, A., & Olson, E. N. (1995) · Genes & Development · doi:10.1101/gad.9.10.1237 · Cited by 351 · see citing works
Self-citationMammalian phylogenomics comes of age
Murphy, W. J., Pevzner, P. A., & O’Brien, S. J. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.09.005 · Cited by 348 · see citing works
Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice
Kothary, R., Clapoff, S., Darling, S. M., Perry, M. D., Moran, L. A., & Rossant, J. (1989) · Development · doi:10.1242/dev.105.4.707 · Cited by 323 · see citing works
Autoregulation and multiple enhancers control Math1 expression in the developing nervous system
Helms, A. W., Abney, A. L., Ben‐Arie, N., Zoghbi, H. Y., & Johnson, J. E. B. (2000) · Development · doi:10.1242/dev.127.6.1185 · Cited by 291 · see citing works
Cserjesi, P., Lilly, B., Bryson, L., Wang, Y., Sassoon, D. A., & Olson, E. N. (1992) · Development · doi:10.1242/dev.115.4.1087 · Cited by 283 · see citing works
Self-citationPrx1 and Prx2 in skeletogenesis: roles in the craniofacial region, inner ear and limbs
ten Berge, D., Brouwer, A., Korving, J., Martin, J. F., & Meijlink, F. C. P. W. (1998) · Development · doi:10.1242/dev.125.19.3831 · Cited by 274 · see citing works
Self-citationA role of Ultrabithorax in morphological differences between Drosophila species
Stern, D. L. (1998) · Nature · doi:10.1038/24863 · Cited by 252 · see citing works
Simmons, N. B., & Geisler, J. H. (1998) · Cited by 233 · see citing works
Colnot, C., Lu, C., Hu, D. P., & Helms, J. A. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.01.011 · Cited by 233 · see citing works
Jeong, Y., El-Jaick, K. B., Roessler, E., Muenke, M., & Epstein, D. J. (2006) · Development · doi:10.1242/dev.02239 · Cited by 227 · see citing works
Development of bat flight: Morphologic and molecular evolution of bat wing digits
Sears, K. E., Behringer, R. R., Rasweiler, J. J., & Niswander, L. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509716103 · Cited by 216 · see citing works
Self-citationRegulatory evolution of shavenbaby/ovo underlies multiple cases of morphological parallelism
Sucena, É., Delon, I., Jones, I. B., Payre, F., & Stern, D. L. (2003) · Nature · doi:10.1038/nature01768 · Cited by 212 · see citing works
Genomic DNA microextraction: A method to screen numerous samples
Ramírez‐Solis, R., Rivera‐Pérez, J. A., Wallace, J. D., Wims, M., Zheng, H., & Bradley, A. (1992) · Analytical Biochemistry · doi:10.1016/0003-2697(92)90347-a · Cited by 212 · see citing works
Drosophila pigmentation evolution: Divergent genotypes underlying convergent phenotypes
Wittkopp, P. J., Williams, B. L., Selegue, J. E., & Carroll, S. B. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0336368100 · Cited by 202 · see citing works
Sucena, É., & Stern, D. L. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.9.4530 · Cited by 201 · see citing works
Enhancers: Mechanisms of Action and Cell Specificity
Atchison, M. L. (1988) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.04.110188.001015 · Cited by 157 · see citing works
Uemura, O., Okada, Y., Ando, H., Guedj, M., Higashijima, S., Shimazaki, T., Chino, N., Okano, H., & Okamoto, H. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.11.031 · Cited by 155 · see citing works
Molecular ontogeny of the skeleton
Eames, B. F., Fuente, L. D. L., & Helms, J. A. (2003) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.10016 · Cited by 148 · see citing works
Cretekos, C. J., Weatherbee, S. D., Chen, C.-H., Badwaik, N. K., Niswander, L. A., Behringer, R. R., & Rasweiler, J. J. (2005) · Developmental Dynamics · doi:10.1002/dvdy.20400 · Cited by 138 · see citing works
Self-citationThe evolution of flight and echolocation in bats: another leap in the dark
Speakman, J. R. (2001) · Mammal Review · doi:10.1046/j.1365-2907.2001.00082.x · Cited by 102 · see citing works
Simmons, N. B., & Geisler, J. H. (1998) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.13520846 · Cited by 100 · see citing works
Transcriptional regulation and the evolution of development
Wray, G. A. (2003) · The International Journal of Developmental Biology · doi:10.1387/ijdb.14756343 · Cited by 93 · see citing works
Pappu, K. S., Ostrin, E. J., Middlebrooks, B. W., Tavsanli, B. C., Chen, R., Atkins, M., Gibbs, R. A., & Mardon, G. (2005) · Development · doi:10.1242/dev.01869 · Cited by 79 · see citing works
Fay, D. S., & Han, M. (2000) · genesis · doi:10.1002/(sici)1526-968x(200004)26:4 · Cited by 66 · see citing works
Xiong, N., Kang, C., & Raulet, D. H. (2002) · Immunity · doi:10.1016/s1074-7613(02)00285-6 · Cited by 65 · see citing works
Maas, S. A., & Fallon, J. F. (2005) · Developmental Dynamics · doi:10.1002/dvdy.20254 · Cited by 54 · see citing works
Rasweiler, J. J., & Badwaik, N. K. (1996) · Laboratory Animals · doi:10.1258/002367796780865718 · Cited by 35 · see citing works
Self-citationCretekos, C. J., Rasweiler, J. J., & Behringer, R. R. (2002) · Reproduction Fertility and Development · doi:10.1071/rd01115 · Cited by 28 · see citing works
Self-citationEvolution of regulatory elements producing a conserved gene expression pattern in Caenorhabditis
Wang, X., Greenberg, J. F., & Chamberlin, H. (2004) · Evolution & Development · doi:10.1111/j.1525-142x.2004.04029.x · Cited by 27 · see citing works
Chesterman, E. S., Gainey, G. D., Varn, A. C., Peterson, R. E., & Kern, M. J. (2001) · Developmental Dynamics · doi:10.1002/dvdy.1198 · Cited by 26 · see citing works
Role of the Intronic Elements in the Endogenous Immunoglobulin Heavy Chain Locus
Wiersma, E. J., Ronai, D., Berrú, M., Tsui, F. W. L., & Shulman, M. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.8.4858 · Cited by 22 · see citing works
The use of composite taxa in supermatrices
Springer, M. S., Scally, M., Madsen, O., JONG, W. W. D., Douady, C. J., & Stanhope, M. J. (2003) · Molecular Phylogenetics and Evolution · doi:10.1016/j.ympev.2003.09.019 · Cited by 19 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Ausubel, F.M. 1989. Current protocols in molecular biology. John Wiley & Sons, New York.
Cited by
Sorted by citations
Evo-Devo and an Expanding Evolutionary Synthesis: A Genetic Theory of Morphological Evolution
Carroll, S. B. (2008) · Cell · doi:10.1016/j.cell.2008.06.030 · Cited by 2,067 · see citing works
Cis-regulatory elements: Molecular mechanisms and evolutionary processes underlying divergence
Wittkopp, P. J., & Kalay, G. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3095 · Cited by 1,231 · see citing works
Ever-Changing Landscapes: Transcriptional Enhancers in Development and Evolution
Long, H. K., Prescott, S. L., & Wysocka, J. (2016) · Cell · doi:10.1016/j.cell.2016.09.018 · Cited by 945 · see citing works
Phenotypic robustness conferred by apparently redundant transcriptional enhancers
Frankel, N., Davis, G. K., Vargas, D., Wang, S., Payre, F., & Stern, D. L. (2010) · Nature · doi:10.1038/nature09158 · Cited by 510 · see citing works
The evolution of hierarchical gene regulatory networks
Erwin, D. H., & Davidson, E. H. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2499 · Cited by 454 · see citing works
Evolution of Gene Regulatory Networks Controlling Body Plan Development
Peter, I. S., & Davidson, E. H. (2011) · Cell · doi:10.1016/j.cell.2011.02.017 · Cited by 417 · see citing works
Progressive Loss of Function in a Limb Enhancer during Snake Evolution
Kvon, E. Z., Kamneva, O. K., Melo, U. S., Barozzi, I., Osterwalder, M., Mannion, B. J., Tissières, V., Pickle, C. S., Plajzer-Frick, I., Lee, E. A., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.028 · Cited by 339 · see citing works
Stepwise Modification of a Modular Enhancer Underlies Adaptation in a <i>Drosophila</i> Population
Rebeiz, M., Pool, J. E., Kassner, V. A., Aquadro, C. F., & Carroll, S. B. (2009) · Science · doi:10.1126/science.1178357 · Cited by 249 · see citing works
Shadow Enhancers Are Pervasive Features of Developmental Regulatory Networks
Cannavò, E., Khoueiry, P., Garfield, D. A., Geeleher, P., Zichner, T., Gustafson, E. H., Ciglar, L., Korbel, J. O., & Furlong, E. E. M. (2016) · Current Biology · doi:10.1016/j.cub.2015.11.034 · Cited by 235 · see citing works
Enhancer redundancy in development and disease
Kvon, E. Z., Waymack, R., Gad, M., & Wunderlich, Z. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00311-x · Cited by 227 · see citing works
Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates
Wang, W., Hu, C.-K., Zeng, A., Alegre, D., Hu, D., Gotting, K., Ortega Granillo, A., Wang, Y., Robb, S., Schnittker, R., et al. (2020) · Science · doi:10.1126/science.aaz3090 · Cited by 210 · see citing works
Self-citationKing, L. B., Walum, H., Inoue, K., Eyrich, N. W., & Young, L. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.12.008 · Cited by 191 · see citing works
“Variation in gene expression mediated by cis-REs plays an important role in evolutionary phenotypic change (32, 42-46).”
Lefebvre, V., & Bhattaram, P. (2010) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(10)90008-2 · Cited by 190 · see citing works
Limb development: a paradigm of gene regulation
Petit, F., Sears, K. E., & Ahituv, N. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2016.167 · Cited by 188 · see citing works
Control of RANKL gene expression
O’Brien, C. A. (2009) · Bone · doi:10.1016/j.bone.2009.08.050 · Cited by 164 · see citing works
Long-range regulation at the SOX9 locus in development and disease: Figure 1
Gordon, C. T., Tan, T. Y., Benko, S., FitzPatrick, D. R., Lyonnet, S., & Farlie, P. G. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2009.068361 · Cited by 163 · see citing works
Mechanisms of transcriptional precision in animal development
Lagha, M., Bothma, J. P., & Levine, M. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.03.006 · Cited by 145 · see citing works
Barolo, S. (2012) · BioEssays · doi:10.1002/bies.201100121 · Cited by 136 · see citing works
Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs
López-Rı́os, J., Duchesne, A., Speziale, D., Andrey, G., Peterson, K. A., Germann, P., Ünal, E., Liu, J., Floriot, S., Barbey, S., et al. (2014) · Nature · doi:10.1038/nature13289 · Cited by 115 · see citing works
A general mechanism for conditional expression of exaggerated sexually‐selected traits
Warren, I. A., Gotoh, H., Dworkin, I. M., Emlen, D. J., & Lavine, L. C. (2013) · BioEssays · doi:10.1002/bies.201300031 · Cited by 103 · see citing works
Piazza, P., Bailey, C. D., Cartolano, M., KRIEGER, J. D., Cao, J., Ossowski, S., Schneeberger, K., He, F., de Meaux, J., Hall, N., et al. (2010) · Current Biology · doi:10.1016/j.cub.2010.11.037 · Cited by 100 · see citing works
Menke, D. B., Guenther, C. A., & Kingsley, D. M. (2008) · Development · doi:10.1242/dev.017384 · Cited by 93 · see citing works
Morphology and behaviour: functional links in development and evolution
Bertossa, R. C. (2011) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2011.0035 · Cited by 92 · see citing works
Ecology: Gene tweaking for conservation
Thomas, M. A., Roemer, G. W., Donlan, C. J., Dickson, B. G., Matocq, M. D., & Malaney, J. L. (2013) · Nature · doi:10.1038/501485a · Cited by 89 · see citing works
Kindlin-2 regulates mesenchymal stem cell differentiation through control of YAP1/TAZ
Guo, L., Cai, T., Chen, K., Wang, R., Wang, J., Cui, C., Yuan, J., Zhang, K., Liu, Z., Deng, Y., et al. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201612177 · Cited by 87 · see citing works
Roscito, J. G., Sameith, K., Parra, G., Langer, B. E., Petzold, A., Moebius, C., Bickle, M., Rodrigues, M. T., & Hiller, M. (2018) · Nature Communications · doi:10.1038/s41467-018-07122-z · Cited by 84 · see citing works
DNA-guided transcription factor cooperativity shapes face and limb mesenchyme
Kim, S., Morgunova, E. Y., Naqvi, S., Goovaerts, S., Bader, M., Koska, M., Popov, A. N., Luong, C., Pogson, A. N., Swigut, T., et al. (2024) · Cell · doi:10.1016/j.cell.2023.12.032 · Cited by 81 · see citing works
Transcriptomic and epigenomic characterization of the developing bat wing
Eckalbar, W. L., Schlebusch, S. A., Mason, M. K., Gill, Z., Parker, A. V., Booker, B. M., Nishizaki, S. S., Nday, C. M., Terhune, E., Nevonen, K. A., et al. (2016) · Nature Genetics · doi:10.1038/ng.3537 · Cited by 80 · see citing works
The Same Regulatory Point Mutation Changed Seed-Dispersal Structures in Evolution and Domestication
Arnaud, N., Lawrenson, T., Østergaard, L., & Sablowski, R. W. M. (2011) · Current Biology · doi:10.1016/j.cub.2011.06.008 · Cited by 79 · see citing works
Evolution of transcriptional enhancers and animal diversity
Rubinstein, M., & de Souza, F. S. J. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0017 · Cited by 78 · see citing works
cis‐regulatory mutations are a genetic cause of human limb malformations
VanderMeer, J. E., & Ahituv, N. (2011) · Developmental Dynamics · doi:10.1002/dvdy.22535 · Cited by 73 · see citing works
Bat accelerated regions identify a bat forelimb specific enhancer in the HoxD locus
Booker, B. M., Friedrich, T., Mason, M. K., VanderMeer, J. E., Zhao, J., Eckalbar, W. L., Logan, M., Illing, N., Pollard, K. S., & Ahituv, N. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1005738 · Cited by 66 · see citing works
Reverse genetics in eukaryotes
Hardy, S., Legagneux, V., Audic, Y., & Paillard, L. (2010) · Biology of the Cell · doi:10.1042/bc20100038 · Cited by 72 · see citing works
Physiological inputs regulate species-specific anatomy during embryogenesis and regeneration
Sullivan, K. G., Emmons‐Bell, M., & Levin, M. G. (2016) · Communicative & Integrative Biology · doi:10.1080/19420889.2016.1192733 · Cited by 72 · see citing works
Enhancers: From Developmental Genetics to the Genetics of Common Human Disease
Williamson, I., Hill, R. E., & Bickmore, W. A. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.06.008 · Cited by 71 · see citing works
Stern, D. L. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.09.006 · Cited by 65 · see citing works
From the ultrasonic to the infrared: molecular evolution and the sensory biology of bats
Jones, G., Teeling, E. C., & Rossiter, S. J. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00117 · Cited by 65 · see citing works
Rogers, W. A., Salomone, J. R., Tacy, D. J., Camino, E. M., Davis, K. A., Rebeiz, M., & Williams, T. M. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003740 · Cited by 65 · see citing works
Genes, development, and evolvability in primate evolution
Rolian, C. (2014) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.21409 · Cited by 61 · see citing works
Pathogenic adaptation of intracellular bacteria by rewiring a cis -regulatory input function
Osborne, S. E., Walthers, D., Tomljenovic-Berube, A. M., Mulder, D. T., Silphaduang, U., Duong, N., Lowden, M. J., Wickham, M. E., Waller, R. F., Kenney, L. J., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811669106 · Cited by 58 · see citing works
Nishihara, H., Kobayashi, N., Kimura-Yoshida, C., Yan, K., Bormuth, O., Ding, Q. J., Nakanishi, A., Sasaki, T., Hirakawa, M., Sumiyama, K., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006380 · Cited by 58 · see citing works
Meier, P. S., Bickelmann, C., Scheyer, T. M., Koyabu, D. B., & Sánchez-Villagra, M. R. (2013) · BMC Evolutionary Biology · doi:10.1186/1471-2148-13-55 · Cited by 56 · see citing works
Kratochwil, C. F., & Meyer, A. (2014) · BioEssays · doi:10.1002/bies.201400142 · Cited by 56 · see citing works
Phylogeny, Genes, and Hearing: Implications for the Evolution of Echolocation in Bats
Teeling, E. C., Jones, G., & Rossiter, S. J. (2016) · Springer handbook of auditory research · doi:10.1007/978-1-4939-3527-7_2 · Cited by 55 · see citing works
The Cells that Fill the Bill: Neural Crest and the Evolution of Craniofacial Development
Jheon, A. H., & Schneider, R. A. (2009) · Journal of Dental Research · doi:10.1177/0022034508327757 · Cited by 53 · see citing works
Chavez, D. E., Gronau, I., Hains, T., Dikow, R. B., Frandsen, P. B., Figueiró, H. V., Garcez, F. S., Tchaicka, L., de Paula, R. C., Rodrigues, F. H. G., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2205986119 · Cited by 52 · see citing works
Characterization of Linaria KNOX genes suggests a role in petal‐spur development
Box, M. S., Dodsworth, S., Rudall, P. J., Bateman, R. M., & Glover, B. J. (2011) · The Plant Journal · doi:10.1111/j.1365-313x.2011.04721.x · Cited by 52 · see citing works
Hockman, D., Mason, M. K., Jacobs, D. S., & Illing, N. (2009) · Developmental Dynamics · doi:10.1002/dvdy.21896 · Cited by 52 · see citing works
(PPR), E. P. O. P. P. P. A. T. R., Hernández, A. F., Adriaanse, P., Aldrich, A., Berny, P. J., Čoja, T., Duquesne, S., Gimsing, A. L., Marina, M., Millet, M., et al. (2019) · EFSA Journal · doi:10.2903/j.efsa.2019.5758 · Cited by 52 · see citing works
The Genetic Basis of Rapidly Evolving Male Genital Morphology inDrosophila
Masly, J. P., Dalton, J. E., Srivastava, S., Chen, L., & Arbeitman, M. N. (2011) · Genetics · doi:10.1534/genetics.111.130815 · Cited by 51 · see citing works
Dobreva, M. P., Camacho, J. J., & Abzhanov, A. (2021) · Journal of Experimental Zoology Part B Molecular and Developmental Evolution · doi:10.1002/jez.b.23103 · Cited by 50 · see citing works
Weeds of change: Cardamine hirsuta as a new model system for studying dissected leaf development
Canales, C., Barkoulas, M., Galinha, C., & Tsiantis, M. (2009) · Journal of Plant Research · doi:10.1007/s10265-009-0263-3 · Cited by 50 · see citing works
Kalay, G., & Wittkopp, P. J. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001222 · Cited by 50 · see citing works
Endochondral ossification and the evolution of limb proportions
Rolian, C. (2020) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.373 · Cited by 49 · see citing works
Schwarzer, W., & Spitz, F. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.03.014 · Cited by 49 · see citing works
Using Drosophila pigmentation traits to study the mechanisms of cis-regulatory evolution
Rebeiz, M., & Williams, T. M. (2016) · Current Opinion in Insect Science · doi:10.1016/j.cois.2016.10.002 · Cited by 49 · see citing works
An integrated view of precambrian eumetazoan evolution
Davidson, E. H., & Erwin, D. H. (2009) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2009.74.042 · Cited by 48 · see citing works
Nolte, M. J., Hockman, D., Cretekos, C. J., Behringer, R. R., & Rasweiler, J. J. (2008) · The Anatomical Record · doi:10.1002/ar.20835 · Cited by 48 · see citing works
Self-citationThe Combinatorial Creature: Cortical Phenotypes within and across Lifetimes
Krubitzer, L. A., & Prescott, T. J. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2018.08.002 · Cited by 47 · see citing works
Developmental and genetic origins of murine long bone length variation
Sanger, T. J., Norgard, E. A., Pletscher, L. S., Bevilacqua, M., Brooks, V. R., Sandell, L. J., & Cheverud, J. M. (2010) · Journal of Experimental Zoology Part B Molecular and Developmental Evolution · doi:10.1002/jez.b.21388 · Cited by 46 · see citing works
Jiménez‐Delgado, S., Pascual‐Anaya, J., & García‐Fernàndez, J. (2009) · Briefings in Functional Genomics and Proteomics · doi:10.1093/bfgp/elp029 · Cited by 45 · see citing works
Dispensability of mammalian DNAPreprint
McLean, C. Y., & Bejerano, G. (2008) · Genome Research · doi:10.1101/gr.080184.108 · Cited by 45 · see citing works
Camino, E. M., Butts, J. C., Ordway, A. J., Vellky, J. E., Rebeiz, M., & Williams, T. M. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005136 · Cited by 44 · see citing works
The developmental basis of bat wing muscle
Tokita, M., ABE, T. K., & Suzuki, K. (2012) · Nature Communications · doi:10.1038/ncomms2298 · Cited by 44 · see citing works
UNDER PRESSURE? DENTAL ADAPTATIONS TO TERMITOPHAGY AND VERMIVORY AMONG MAMMALS
Charles, C., Solé, F., Rodrigues, H. G., & Viriot, L. (2013) · Evolution · doi:10.1111/evo.12051 · Cited by 44 · see citing works
Hörnblad, A., Bastide, S., Langenfeld, K., Langa, F., & Spitz, F. (2021) · Nature Communications · doi:10.1038/s41467-020-20714-y · Cited by 44 · see citing works
The Molecular Regulation of Vertebrate Limb Patterning
Butterfield, N. C., McGlinn, E., & Wicking, C. (2010) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(10)90009-4 · Cited by 42 · see citing works
Ovarian Organogenesis in Mammals: Mice Cannot Tell Us Everything
Jiménez, R. (2009) · Sexual Development · doi:10.1159/000280584 · Cited by 41 · see citing works
Cis-regulation and chromosomal rearrangement of the fgf8 locus after the teleost/tetrapod split
Komisarczuk, A. Z., Kawakami, K., & Becker, T. S. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.09.029 · Cited by 41 · see citing works
Krubitzer, L. A., & Dooley, J. C. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00620 · Cited by 41 · see citing works
Integration of the transcriptional networks regulating limb morphogenesis
Rabinowitz, A. H., & Vokes, S. A. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.05.035 · Cited by 40 · see citing works
Creating diversity in mammalian facial morphology: a review of potential developmental mechanisms
Usui, K., & Tokita, M. (2018) · EvoDevo · doi:10.1186/s13227-018-0103-4 · Cited by 40 · see citing works
gga-mir-133a-3p Regulates Myoblasts Proliferation and Differentiation by Targeting PRRX1
Guo, L., Huang, W., Chen, B., Jebessa, E., Chen, X., Cai, B., & Nie, Q. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00577 · Cited by 39 · see citing works
Modeling uniquely human gene regulatory function via targeted humanization of the mouse genome
Dutrow, E. V., Emera, D., Yim, K., Uebbing, S., Kocher, A. A., Krenzer, M., Nottoli, T., Burkhardt, D. B., Krishnaswamy, S., Louvi, A., et al. (2022) · Nature Communications · doi:10.1038/s41467-021-27899-w · Cited by 39 · see citing works
The evolution and development of mammalian flight
Cooper, L. N., Cretekos, C. J., & Sears, K. E. (2012) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.50 · Cited by 38 · see citing works
Self-citationUnique expression patterns of multiple key genes associated with the evolution of mammalian flight
Wang, Z., Dai, M., Wang, Y., Cooper, K. L., Zhu, T., Dong, D., Zhang, J., & Zhang, S. Y. (2014) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2013.3133 · Cited by 38 · see citing works
Self-citationWing bone laminarity is not an adaptation for torsional resistance in bats
Lee, A. H., & Simons, E. L. R. (2015) · PeerJ · doi:10.7717/peerj.823 · Cited by 37 · see citing works
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-619 · Cited by 34 · see citing works
Beyond Neuroanatomy: Novel Approaches to Studying Brain Evolution
Pollen, A. A., & Hofmann, H. A. (2008) · Brain Behavior and Evolution · doi:10.1159/000151474 · Cited by 34 · see citing works
Castro, S. D., Peronnet, F., Gilles, J.-F., Mouchel‐Vielh, E., & Gibert, J. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007573 · Cited by 34 · see citing works
The regulation of Dkk1 expression during embryonic development
Lieven, O., Knobloch, J., & Rüther, U. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.01.037 · Cited by 33 · see citing works
Understanding of bat wing evolution takes flightPreprint
Cooper, K. L., & Tabin, C. J. (2008) · Genes & Development · doi:10.1101/gad.1639108 · Cited by 33 · see citing works
Koyabu, D. B., & Sơn, N. T. (2014) · Journal of Experimental Zoology Part B Molecular and Developmental Evolution · doi:10.1002/jez.b.22581 · Cited by 32 · see citing works
The origins, scaling and loss of tetrapod digits
Saxena, A., Towers, M., & Cooper, K. L. (2016) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2015.0482 · Cited by 32 · see citing works
Cooper, L. N., Sears, K. E., Armfield, B. A., Kala, B., Hubler, M. J., & Thewissen, J. G. M. (2017) · genesis · doi:10.1002/dvg.23076 · Cited by 31 · see citing works
Evaluating the probability of CRISPR‐based gene drive contaminating another species
Courtier‐Orgogozo, V., Danchin, A., Gouyon, P., & Boëte, C. (2020) · Evolutionary Applications · doi:10.1111/eva.12939 · Cited by 31 · see citing works
Synthetic Biology: A Bridge Between Functional and Evolutionary Biology
Morange, M. (2009) · Biological Theory · doi:10.1162/biot_a_00003 · Cited by 31 · see citing works
Heterogeneous Tempo and Mode of Conserved Noncoding Sequence Evolution among Four Mammalian Orders
Babarinde, I. A., & Saitou, N. (2013) · Genome Biology and Evolution · doi:10.1093/gbe/evt177 · Cited by 30 · see citing works
The Functionality and Evolution of Eukaryotic Transcriptional Enhancers
Buffry, A. D., Mendes, C. C., & McGregor, A. P. (2016) · Advances in genetics · doi:10.1016/bs.adgen.2016.08.004 · Cited by 30 · see citing works
Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development
Liu, Q., Önal, P., Datta, R. R., Rogers, J. M., Schmidt‐Ott, U., Bulyk, M. L., Small, S., & Thornton, J. W. (2018) · eLife · doi:10.7554/elife.34594 · Cited by 29 · see citing works
Floc’hlay, S., Wong, E. S. W., Zhao, B., Viales, R. R., Thomas‐Chollier, M., Thieffry, D., Garfield, D. A., & Furlong, E. E. M. (2020) · Genome Research · doi:10.1101/gr.266338.120 · Cited by 29 · see citing works
How do we get a perfect complement of digits?
Bastida, M. F., & Ros, M. A. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.06.009 · Cited by 28 · see citing works
Clarifying tetrapod embryogenesis, a physicist's point of view
Fleury, V. (2009) · The European Physical Journal Applied Physics · doi:10.1051/epjap/2009033 · Cited by 28 · see citing works
Regulatory DNAs and the evolution of human development
Noonan, J. P. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.10.002 · Cited by 27 · see citing works
Hosoya-Ohmura, S., Mizuno, S., Oishi, H., Ku, C.-J., Hermann, M., Hosoya, T., Takahashi, S., & Engel, J. D. (2016) · Journal of Clinical Investigation · doi:10.1172/jci83894 · Cited by 27 · see citing works
The emerging roles of eRNAs in transcriptional regulatory networks
Mousavi, K., Zare, H., Koulnis, M., & Sartorelli, V. (2014) · RNA Biology · doi:10.4161/rna.27950 · Cited by 27 · see citing works
McGaughey, D. M., Stine, Z. E., Huynh, J. L., Vinton, R. M., & McCallion, A. S. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-8 · Cited by 26 · see citing works
A complex regulatory landscape involved in the development of mammalian external genitals
Amândio, A. R., Lopez‐Delisle, L., Bolt, C. C., Mascrez, B., & Duboule, D. (2020) · eLife · doi:10.7554/elife.52962 · Cited by 26 · see citing works
Functional analysis of limb transcriptional enhancers in the mouse
Nolte, M. J., Wang, Y., Deng, J. M., Swinton, P. G., Wei, C., Guindani, M., Schwartz, R. J., & Behringer, R. R. (2014) · Evolution & Development · doi:10.1111/ede.12084 · Cited by 25 · see citing works
Self-citationTiming the developmental origins of mammalian limb diversity
Sears, K. E., Maier, J. A., Sadier, A., Sorensen, D. W., & Urban, D. J. (2017) · genesis · doi:10.1002/dvg.23079 · Cited by 25 · see citing works
- Authors
- Cretekos, C. J., Wang, Y., Green, E. D., Program, N. C. S., Martin, J. F., Rasweiler, J. J., & Behringer, R. R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- National Institutes of Health (US)
- Texas A&M University (US)
- Texas A&M Health Science Center (US)
- SUNY Downstate Health Sciences University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-01-15
- Volume
- 22
- Issue
- 2
- Pages
- 141-151
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2192750
- OpenAlex
- W2138279862
- Cited by
- 232
- References
- 54
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 15 · 2020: 19 · 2019: 4 · 2018: 10 · 2017: 11 · 2016: 20 · 2015: 10 · 2014: 22 · 2013: 14 · 2012: 12
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0220458)
- National Institutes of Health (CA-16 672, HD07325)
- National Human Genome Research Institute
- National Cancer Institute (CA 09299, T32CA009299, P30CA016672)
- National Institute of Dental and Craniofacial Research (DE16329, R01DE016329)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007325, HD 16672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Physical Sciences › Mathematics › Geometry and Topology › Morphological variations and asymmetry
- Keywords
- limb length, PRRX1, enhancers, cis-regulatory elements, regulatory divergence, forelimb development, endochondral ossification, mice, morphological evolution
- MeSH terms
- Animals, Chiroptera, Enhancer Elements, Genetic, Biological Evolution, Forelimb, Gene Expression Regulation, Genes, Homeobox, Mutation, Regulatory Sequences, Nucleic Acid, Transfection, Homeodomain Proteins, Evolution, Molecular, Mice
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