David Gardiner, Ph.D.

Limb development and regeneration – How to Regenerate a New Leg: What we can learn from salamanders – Alone among vertebrates, urodele amphibians are able to regenerate lost body parts as adults. The key to this ability is that limb cells are triggered to dedifferentiate and reinitiate growth and pattern formation. Our strategy is to use axolotls (Ambystoma mexicanum) to discover the signals that trigger the regeneration response, in the belief that these signals have enormous potential and consequences for human health. Our long term goals are to identify the regeneration-enabling signals in limbs, in order to support progress towards the eventual application of these molecules to the improvement of human repair mechanisms. In current research, we are using assays derived from the extensive experimental history of regenerating limbs, to test the roles of several signaling molecules known to be essential for limb development …

Recent Publications

  • Gardiner, D.M. (2017). Recurrent concepts. In: Regenerative Engineering and Developmental Biology: Principles and Applications. D.M. Gardiner (ed). CRC Press, Boca Raton FL pp. 598-608.
  • Bryant, S.V. and Gardiner, D.M. (2017). The positional information grid in development and regeneration. In: Regenerative Engineering and Developmental Biology: Principles and Applications. D.M. Gardiner (ed). CRC Press, Boca Raton FL pp. 327-350.
  • Gardiner, D.M. (2017). The role of nerves in the regulation of regeneration. In: Regenerative Engineering and Developmental Biology: Principles and Applications. D.M. Gardiner (ed). CRC Press, Boca Raton FL pp. 113-137.
  • Gardiner, D.M. (2017). Introduction to regenerative engineering and developmental biology. In: Regenerative Engineering and Developmental Biology: Principles and Applications. D.M. Gardiner (ed). CRC Press, Boca Raton FL pp. 1-19.
  • Seyedhassantehrani, N., Otsuka, T., Singh, S., and Gardiner, D.M. (2017). The axolotl limb regeneration model as a discovery tool for engineering the stem cell niche. Curr. Stem Cell Reports. 3:156163. DOI 10.1007/s40778-017-0085-5
  • Gardiner, D.M. (2017). Regulation of regeneration by heparan sulfate proteoglycans in the extracellular matrix. Regenerative Engineering and Translational Medicine (Springer). 3:192-198. DOI: 1007/s40883-017-0037-8
  • McCusker, C., Diaz-Castillo, C., Sosnik, J., Phan, A.Q., and Gardiner, D.M. (2016). Histological image data of limb skeletal tissue from larval and adult Ambystoma mexicanum, Data in Brief. 8: 1206-1208. http://dx.doi.org/10.1016/j. dib.2016.07.028i
  • McCusker, C., Diaz-Castillo, C., Sosnik, J., Phan, A.Q., and Gardiner, D.M. (2016). Cartilage and bone cells do not participate in skeletal regeneration in Ambystoma mexicanum limbs. Dev. Biol. 416: 26-33. PMID: 27316294.
  • Bryant, S.V. and Gardiner, D.M. (2016). The relationship between growth and pattern formation. REGENERATION. 3:103-122. PMID: 27499882.
  • McCusker, C., Athippozhy, A., Diaz-Castillo, C., Fowlkes, C., Gardiner, DM., and Voss, SR. (2015). Positional plasticity in regenerating Ambystoma Mexicanum limbs is associated with cell proliferation and pathways of cellular differentiation. BMC Dev. Biol. 15: 45 – 62. PMID 26597593
  • Aguilar, C. and Gardiner, D. M. (2015). DNA methylation dynamics regulate the formation of a regenerative wound epithelium during axolotl limb regeneration. PLoS One, 2015, 10(8): e0134791. doi:10.1371/journal.pone.0134791.
  • Phan, A.Q., Lee, J., Oei, M., Flath, C., Hwe, C., Mariano, R., Vu, T, Shu, C., Muneoka, K., Bryant, S.V., and Gardiner, D.M. (2015) Heparan Sulfates Mediate Positional Information by Position-Specific Growth Factor Regulation during Axolotl (Ambystoma mexicanum) Limb Regeneration. REGENERATION. 2015 August 11, DOI: 10.1002/reg2.40.
  • McCusker, C., Gardiner, D.M and Bryant, S.V. (2015). The Axolotl limb blastema: cellular and molecular mechanisms driving blastema formation and limb regeneration in tetrapods. REGENERATION. 2015 May 11, DOI: 10.1002/reg2.32
  • Lehrberg, J. and Gardiner, D.M. (2015). Regulation of axolotl (Ambystoma mexicanum) limb blastema cell proliferation by nerves and BMP2. PLoS One. 2015, PONE-D-14-52826.
  • Endo, T., Gardiner, D.M., Makanae, A., and Satoh, A. (2015). The Accessory Limb Model: An alternative experimental system of limb regeneration. Meth. Mol. Biol. 1290:101-113.
  • Voss, R., Palumbo, A., Nagarajan, R., Gardiner, D.M., Muneoka, K., Stromberg, A., Athipopozhy, A. Gene Expression During the First 28 Days of Axolotl Limb Regeneration I: Experimental Design and Global Analysis of Gene Expression (2015). REGENERATION. 2015 June 19, DOI: 10.1002/reg2.37
  • McCusker, C. and Gardiner, D.M. (2014). Understanding positional cues in salamander limb regeneration: implications for optimizing cell-based regenerative therapies. Disease Models & Mechanisms. 7: 593-599.
  • Athippozhy, A., Lehberg, J., Monaghan, J. R., Tsai, S., Gardiner, D. M., and Voss S.R. (2014). Characterization of in vitro transcriptional responses of dorsal root ganglia cultured in the presence and absence of blastema cells from regenerating salamander limbs. REGENERATION. 2014 July 4, DOI: 10.1002/reg2.14
  • McCusker, C, Lehrberg, J. and Gardiner, D.M. (2014) Position-specific induction of ectopic limbs in non-regenerating blastemas on Axolotl forelimbs. REGENERATION. 2014 Feb 16, DOI: 10.1002/reg2.10.
  • McCusker, C. and Gardiner, D.M. (2013) Positional information is reprogrammed in blastema cells of the regenerating axolotl limb. PLoS One, 2013 Sep 27;8(9):e77064. PMID: 24086768
  • Gardiner, D.M., Bryant, S.V. and Muneoka, K. (2013). Engineering a regenerated limb. In: Regenerative Engineering (Laurencin, C and Kahn, Y. eds). CRC Press, New York. Pp. 387-404.
  • Jangwoo Lee, Amy Corcoran, Manjong Han, Gardiner, D.M. and Ken Muneoka(2013). Dlx5 and Msx2 Regulate Mouse Anterior Neural Tube Closure through ephrinA5-EphA7. Dev. Growth Diff. 55:341-349. PMID: 23425387
  • Lee, J., Aguilar, C. and Gardiner, D.M. (2013). Gain-of-function assays in the axolotl (Ambystoma mexicanum) to identify signaling pathways that induce and regulate limb regeneration. In: Wound Regeneration and Repair, Methods and Protocols (Gourdie, R.G. and Myers, T.A. eds.) Humana Press, New York. Pp. 401-417.
  • Lee, J. and Gardiner, D.M. (2012). Regeneration of limb joints in the axolotl (Ambystoma mexicanum). PLoS One 7:1-9. PMID: 23185640
  • Zhu, W., Kuo, D., Nathanson, J., Satoh, A., Pao, G.M., Yeo, G.W., Bryant, S.V., Voss, S.R., Gardiner, D.M., and Hunter, T. (2012). Retrotransposon long interspaced nucleotide element-1 is activated during salamander limb regeneration. Dev. Growth Diff. 54:673-685. PMID: 22913491.
  • Zhu, W., Pao, G. M., Satoh, A., Cummings G., Monaghan, J.R., Harkins, T.T., Bryant, S.V., Voss, S.R., Gardiner, D.M., and Hunter, T. (2012). Activation of germline-specific genes is required for limb regeneration in the Mexican axolotl. Dev. Biol. 379:423-51. PMID: 22841627.
  • Satoh A., Bryant, S.V. and Gardiner, D.M. (2012). Nerve signaling regulates basal keratinocyte proliferation in the blastema apical epithelial cap in the axolotl (Ambystoma mexicanum). Dev. Biol. 366: 374-381. PMID: 22537500.
  • Monaghan, J.R., Athippozhy, A., Seifer, A.W., Putta, S., Stromberg, A., Maden, M., Gardiner, D.M. and Voss, S.R. (2012). Gene expression patterns specific to the regenerating limb of the Mexican axolotl. Biology Open 1 :937-948. PMID: 23213371
  • Gardiner, D.M. and Holmes, L.B. (2012). Hypothesis: Terminal transverse limb defects with “Nubbins” represent a regenerative process during limb development in human fetuses. Birth Defects Research 94:129-133. PMID: 22287196.
  • Sun, L., Chen, M., Yang, H., Wang, T., Liu, B., Shu, C. and David M. Gardiner, D.M. (2011). 454 sequencing analysis of gene expression profiling during Intestinal and body wall regeneration in the sea cucumber. Comp. Biochem. Physiol. Part D Genomics Proteomics 6:195-205. PMID: 21501978.
  • McCusker, C. and Gardiner, D.M. (2011). The axolotl model for regeneration and aging research: A Mini-Review. Gerontology. 57:565-571. PMID: 21372551.
  • Satoh, A., Cummings, G.M.C., Bryant, S.V. and Gardiner, D.M. (2010). Regulation of proximal-distal intercalation during limb regeneration in the axolotl (Ambystoma mexicanum). Dev. Growth Diff. 52: 785-798. PMID: 21158757.
  • Ferris, D.R., Satoh, A., Mandefro, B., Cummings, G., Gardiner, D.M. and Rugg, E.L. (2010). Ex vivo generation of a functional and regenerative wound epithelium from axolotl (Ambystoma mexicanum) skin. Dev. Growth Diff. 52:715-724. PMID: 20874715.
  • Hirata, A., Gardiner, D.M., and Satoh, A. (2010). Dermal fibroblasts contribute to multiple tissues in the accessory limb model. Dev. Growth & Diff. 52:343-50.
  • Satoh, A., Cummings, G.M.C., Bryant, S.V., and Gardiner, D.M. (2010). Neurotrophic regulation of fibroblast dedifferentiation during limb skeletal regeneration in the axolotl (Ambystoma mexicanum). Dev. Biol. 337:444-457.
  • Smith, J.J., Putta, S., Zhu, W., Pao,. G., Harkins, T., Hunter, T., Verma, I., Bryant, S.V., Gardiner, D.M., and Voss, S.R. (2009). Genic Regions of a Large Salamander Genome Contain Long Introns and Novel Genes. BMC Genomics 10:19-29.
  • Tanner K, Ferris DR, Lanzano L, Mandefro B, Mantulin WW, Gardiner DM, Rugg EL, Gratton E.. (2009) Coherent Movement of Cell Layers During Wound Healing by Image Correlation Spectroscopy. Biophysical J. 97:2098-2106.
  • Holden, P.K., Li, C., Da Costa, V., Sun, C.H., Bryant, S.V., Gardiner, D.M., and Wong, B.J.F. (2009). The effects of laser irradiation of cartilage on chondrocyte gene expression and the collagen matrix. Lasers in Surgery & Medicine 41:487-491.
  • Satoh, A., James, M.A. and Gardiner, D.M. (2009). The role of nerve signaling in limb genesis and agenesis during axolotl limb regeneration. J. Bone Joint Surg. 91:90-98.
  • Monaghan, J.R., Epp, L., Putta, S., Page, R.B., Walker, J.A., Beachy, C.K., Zhu, W., Pao, G.M., Verma, I.M., Hunter, T., Bryant, S.V., Gardiner, D.M., Harkins, T.T., and Voss, S.R. (2009). Microarray and cDNA sequence analysis of transcription during nerve-dependent limb regeneration. BMC Biology 7:1-19.
  • Satoh, A., Bryant, S.V. and Gardiner, D.M. (2008). Regulation of dermal fibroblast dedifferentiation and redifferentiation during wound healing and limb regeneration in the Axolotl. Dev. Growth & Diff. 50:743-754. PMID: 19046162.
  • Satoh, A., Graham, G.M.C., Bryant, S.V. and Gardiner, D.M. (2008). Neurotrophic regulation of epidermal dedifferentiation during wound healing and limb regeneration in the axolotl (Ambystoma mexicanum). Dev. Biol. 319:321-325.
  • Ghosh, S., Roy, S., Seguin, C., Bryant, S.V. and Gardiner, D.M. (2008). Expression of Wnt5a and Wnt5b in developing and regenerating axolotl limbs. Dev. Growth & Diff. 50:289-297
  • Muneoka, K., Han, M., and Gardiner, D. (2008). Human Limb Regeneration: Understanding the Challenge. Scientific American 298:56-63.
  • Satoh, A., Gardiner, D.M., Bryant, S.V. and Endo, T. (2007). Nerve-induced ectopic limb blastemas in the axolotl are equivalent to amputation-induced blastemas. Dev. Biol. 312:231-244.
  • Gardiner, D.M. and Bryant, S.V. (2007). Homeobox-containing genes in limb regeneration. in “HOX Gene Expression” (ed. Spyros Papageorgiou). Landes Bioscience, Austin. 9 pp
  • Grun, F., Watanabe, H., Zamanian, Z., Maeda, L. Arima, K., Chubacha, R., Gardiner, D.M., Kanno, J., Iguchi, T., and Blumberg, B. (2006). Endocrine disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Mol Endocrinol. 20: 2141-2155.
  • Gardiner, D.M. and Susan V. Bryant (2006). Limb Regeneration. in “Fins into Limbs”, Brian Hall (ed.). Univ. Chicago Press. Chicago
  • Wong, B.J.F., Pandhoh, N., Truong, M.T., Diaz, S., Chao, K., Hou, S. and Gardiner, D.M. (2005). Identification of chondrocyte proliferation following laser irradiation, thermal injury, and mechanical trauma. Lasers in Surgery & Medicine. 37:89-96.
  • Gardiner, D.M. (2005). Ontogenetic decline of regenerative ability and the stimulation of human regeneration. Rejuvenation Res. 8:141-153.
  • Putta, S., Smith, J.J., Walker, J., Rondet, M., Weisrock, D.W., Monaghan, J., Samuels, A.K., Kump, K., King, D.C., Maness, N.J., Habermann, B., Tanaka, E., Bryant, S.V., Gardiner, D.M., Parichy, D.M. and Voss, S.R. (2004). From Biomedicine to Natural History Research: Expressed Sequence Tag Resources for Ambystomatid Salamanders. BMC Genomics 5:54-70.
  • Endo, T., Bryant, S.V., and Gardiner, D.M. (2004). A stepwise model system for limb regeneration. (2004). Dev. Biol. 270:135-145.

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