Ken Muneoka

• Cell Biology

Dr. Muneoka’s research is focused on discovering ways to enhance regenerative capabilities of mammalian limbs. His early studies using the amphibian limb as a regeneration model provided the first direct evidence that the process of limb regeneration involved the reutilization of developmental processes. Dr. Muneoka pioneered the study of regenerative capabilities of embryonic mice by developing microsurgical procedures for manipulating mid-gestational stage embryos in utero. Dr. Muneoka’s cumulative work on regeneration in higher vertebrate models has illuminated a road map for tackling the intractable problem of how to induce regenerative responses in mammals. Using the mouse digit tip as a regeneration model, a number of key signaling pathways have been identified as critical for mammalian blastema formation and regeneration, while gain of function studies using non-regenerating digit or limb amputations provide clear examples of how activation of these signaling pathways can induce regenerative responses. Most recently, Dr. Muneoka’s lab has demonstrated that mammalian joints can be induced to regenerate and this has led to in vitro strategies for differentiating articular cartilage that can be used for surgically repair damaged joints.

Ken Muneoka is accepting trainees of these groups:

• Undergraduate Scholars

Lab Members

Conor Dolan: Connor received his undergraduate training in Neuroscience at Tulane University and is now doing his PhD in the laboratory of Dr. Ken Muneoka. His project focuses on understanding the interactions between peripheral nerves and mechanical loading in the context of digit tip regeneration.

Yu-Lieh Lin is now doing his PhD in the laboratory of Dr. Ken Muneoka. His thesis project focuses on investigating the possibility to differentiate mouse adipose stem cells into hyaline cartilage in vitro and determine the repair efficacy of these differentiated cells in articular cartilage defected mice.

Evolution of epimorphosis in mammals (2020) Journal of Experimental Zoology Part B: Molecular and Developmental Evolution 10.1002/jez.b.22925

Sirtuin 3 deficiency does not impede digit regeneration in mice. (2019) Scientific reports 10.1038/s41598-019-52921-z

Adult Mouse Digit Amputation and Regeneration: A Simple Model to Investigate Mammalian Blastema Formation and Intramembranous Ossification (2019) Journal of Visualized Experiments 10.3791/59749

BMP9 stimulates joint regeneration at digit amputation wounds in mice. (2019) Nature communications 10.1038/s41467-018-08278-4

Axonal regrowth is impaired during digit tip regeneration in mice. (2018) Developmental biology 10.1016/j.ydbio.2018.11.010

Blastema formation and periosteal ossification in the regenerating adult mouse digit. (2018) Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 10.1111/wrr.12666

Digit Tip Regeneration: Merging Regeneration Biology with Regenerative Medicine (2018) STEM CELLS Translational Medicine 10.1002/sctm.17-0236

The Impact of Aging on Mechanisms of Mammalian Epimorphic Regeneration. (2018) Gerontology 10.1159/000485320

The blastema and epimorphic regeneration in mammals. (2017) Developmental biology 10.1016/j.ydbio.2017.08.007

Macrophages are required to coordinate mouse digit tip regeneration (2017) Development 10.1242/dev.150086

The periosteal requirement and temporal dynamics of BMP2-induced middle phalanx regeneration in the adult mouse (2017) Regeneration 10.1002/reg2.81

Fibroblast reticular cells engineer a blastema extracellular network during digit tip regeneration in mice. (2017) Regeneration (Oxford, England) 10.1002/reg2.75

Analogous cellular contribution and healing mechanisms following digit amputation and phalangeal fracture in mice. (2016) Regeneration (Oxford, England) 10.1002/reg2.51

Positional information in axolotl and mouse limb extracellular matrix is mediated via heparan sulfate and fibroblast growth factor during limb regeneration in the axolotl (Ambystoma mexicanum). (2015) Regeneration (Oxford, England) 10.1002/reg2.40

Gene expression during the first 28 days of axolotl limb regeneration I: Experimental design and global analysis of gene expression. (2015) Regeneration (Oxford, England) 10.1002/reg2.37

Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration. (2015) Regeneration (Oxford, England) 10.1002/reg2.34

The mammalian blastema: regeneration at our fingertips. (2015) Regeneration (Oxford, England) 10.1002/reg2.36

Angiogenesis is inhibitory for mammalian digit regeneration. (2014) Regeneration (Oxford, England) 10.1002/reg2.24

Endogenous bone regeneration is dependent upon a dynamic oxygen event (2014) Journal of Bone and Mineral Research 10.1002/jbmr.2261

Connective Tissue Fibroblast Properties Are Position-Dependent during Mouse Digit Tip Regeneration (2013) PLoS ONE 10.1371/journal.pone.0054764

Dlx5 and Msx2 regulate mouse anterior neural tube closure through ephrinA5-EphA7 (2013) Development Growth and Differentiation 10.1111/dgd.12044

SDF-1α/CXCR4 signaling mediates digit tip regeneration promoted by BMP-2 (2013) Developmental Biology 10.1016/j.ydbio.2013.07.020

The mouse digit tip: From wound healing to regeneration (2013) Methods in Molecular Biology 10.1007/978-1-62703-505-7-24

Regeneration of the elbow joint in the developing chick embryo recapitulates development. (2012) Developmental biology 10.1016/j.ydbio.2012.09.020

BMP2 induces segment-specific skeletal regeneration from digit and limb amputations by establishing a new endochondral ossification center (2012) Developmental Biology 10.1016/j.ydbio.2012.09.021

Regenerative phenotype in mice with a point mutation in transforming growth factor β type I receptor (TGFBR1) (2011) Proceedings of the National Academy of Sciences of the United States of America 10.1073/pnas.1111056108

Wound healing and blastema formation in regenerating digit tips of adult mice (2011) Developmental Biology 10.1016/j.ydbio.2010.11.035

BMP signaling induces digit regeneration in neonatal mice (2010) Development 10.1242/dev.042424

In Utero and Exo Utero Surgery on Rodent Embryos (2010) Methods in Enzymology 10.1016/S0076-6879(10)76012-2

Development and regeneration of the neonatal digit tip in mice (2008) Developmental Biology 10.1016/j.ydbio.2007.12.025

Mammalian regeneration and regenerative medicine (2008) Birth Defects Research Part C - Embryo Today: Reviews 10.1002/bdrc.20137

Mouse embryonic diastema region is an ideal site for the development of ectopically transplanted tooth germ (2008) Developmental Dynamics 10.1002/dvdy.21427

Regrowing human limbs (2008) Scientific American 10.1002/dvdy.21427

Shox2 is required for chondrocyte proliferation and maturation in proximal limb skeleton (2007) Developmental Biology 10.1016/j.ydbio.2007.03.518

Limb regeneration in higher vertebrates: Developing a roadmap (2005) Anatomical Record - Part B New Anatomist 10.1002/ar.b.20082

Digit regeneration is regulated by Msx1 and BMP4 in fetal mice (2003) Development 10.1242/dev.00710

Differential cell affinity and sorting of anterior and posterior cells during outgrowth of recombinant avian limb buds (2002) Developmental Biology 10.1016/S0012-1606(02)90804-3

Cell biology limb patterning (2001) International Review of Cytology 10.1016/S0012-1606(02)90804-3

Inhibition of polarizing activity in the anterior limb bud is regulated by extracellular factors (2001) Developmental Biology 10.1006/dbio.2001.0500

Evalaution of biologically based dose-response modeling for developmental toxicity: A workshop report (2000) Regulatory Toxicology and Pharmacology 10.1006/rtph.1999.1360

Exo utero surgery. (2000) Methods in molecular biology (Clifton, N.J.) 10.1006/rtph.1999.1360

Influence of FGF4 on digit morphogenesis during limb development in the mouse (2000) Developmental Biology 10.1006/dbio.2000.9612

Cell migration and chick limb development: Chemotactic action of FGF-4 and the AER (1999) Developmental Biology 10.1006/dbio.1999.9317

Regeneration in higher vertebrates: Limb buds and digit tips (1999) Seminars in Cell and Developmental Biology 10.1006/scdb.1999.0327

FGF-2 influences cell movements and gene expression during limb development (1996) Journal of Experimental Zoology 10.1006/scdb.1999.0327

Digit tip regeneration correlates with regions of Msx1 (Hox 7) expression in fetal and newborn mice (1995) Development 10.1006/scdb.1999.0327

Conversion of anterior limb bud cells to ZPA signaling cells in vitro and in vivo (1994) Developmental Biology 10.1006/dbio.1994.1195

FGF-2 induces regeneration of the chick limb bud (1994) Developmental Biology 10.1006/dbio.1994.1144

Regeneration of HoxD expression domains during pattern regulation in chick wing buds (1994) Developmental Biology 10.1006/dbio.1994.1048

3T3 cell integration and differentiative potential during limb development in the mouse (1993) Developmental Biology 10.1006/dbio.1993.1004

In vitro maintenance of posterior (ZPA) signaling in mouse limb bud cells. (1993) Progress in clinical and biological research 10.1006/dbio.1993.1004

MPLB-2: a posterior signaling cell line derived from the mouse limb bud. (1993) Progress in clinical and biological research 10.1006/dbio.1993.1004

Maintenance of ZPA signaling in cultured mouse limb bud cells (1993) Development 10.1006/dbio.1993.1004

Molecular aspects of regeneration in developing vertebrate limbs (1992) Developmental Biology 10.1016/0012-1606(92)90154-9

Position specific growth regulation of 3T3 cells in vivo (1992) Developmental Biology 10.1016/0012-1606(92)90008-5

Position-specific growth of mouse limb bud cells in vitro (1992) Developmental Biology 10.1016/0012-1606(92)90208-X

Conversion by retinoic acid of anterior cells into ZPA cells in the chick wing bud (1991) Nature 10.1038/350081a0

Mapping the early development of projections from the entorhinal cortex in the embryonic mouse using prenatal surgery techniques (1991) Journal of Neurobiology 10.1038/350081a0

A staging system for mouse limb development (1989) Journal of Experimental Zoology 10.1038/350081a0

Evidence for regulation following amputation and tissue grafting in the developing mouse limb. (1989) Journal of Experimental Zoology 10.1038/350081a0

Mammalian limb bud development: in situ fate maps of early hindlimb buds. (1989) Journal of Experimental Zoology 10.1038/350081a0

Intercalation and the cellular origin of supernumerary limbs in Xenopus (1987) Development 10.1038/350081a0

Limb development and regeneration (1987) Integrative and Comparative Biology 10.1093/icb/27.2.675

Cellular contribution from dermis and cartilage to the regenerating limb blastema in axolotls (1986) Developmental Biology 10.1016/0012-1606(86)90062-X

Exo utero survival of mouse embryos. (1986) Progress in clinical and biological research 10.1016/0012-1606(86)90062-X

Intrinsic control of regenerative loss in Xenopus laevis limbs (1986) Journal of Experimental Zoology 10.1016/0012-1606(86)90062-X

Mouse embryos develop normally exo utero (1986) Journal of Experimental Zoology 10.1016/0012-1606(86)90062-X

Pattern discontinuity, polarity and directional intercalation in axolotl limbs (1986) Journal of Embryology and Experimental Morphology 10.1016/0012-1606(86)90062-X

Regeneration from discontinuous circumferences in axolotl limbs. (1986) Progress in clinical and biological research 10.1016/0012-1606(86)90062-X

The migration of dermal cells during blastema formation in axolotls (1986) Developmental Biology 10.1016/0012-1606(86)90020-5

Views of limb development and regeneration (1986) Trends in Genetics 10.1016/0168-9525(86)90210-6

A quantitative analysis of regeneration from chimaeric limb stumps in the axolotl (1985) Journal of Embryology and Experimental Morphology 10.1016/0168-9525(86)90210-6

Cellular contribution to supernumerary limbs in the axolotl, Ambystoma mexicanum (1984) Developmental Biology 10.1016/0012-1606(84)90272-0

Cellular contribution to supernumerary limbs resulting from the interaction between developing and regenerating tissues in the axolotl (1984) Developmental Biology 10.1016/0012-1606(84)90273-2

Improved techniques for use of the triploid cell marker in the axolotl, Ambystoma mexicanum (1984) Developmental Biology 10.1016/0012-1606(84)90280-X

Do chick limb bud cells have positional information? (1983) Progress in clinical and biological research 10.1016/0012-1606(84)90280-X

Evidence that patterning mechanisms in developing and regenerating limbs are the same (1982) Nature 10.1016/0012-1606(84)90280-X

A new method for mechanical dechorionation of ascidian eggs (1980) Developmental Biology 10.1016/0012-1606(80)90448-0