BMP signaling induces digit regeneration in neonatal mice.
The regenerating digit tip of mice is a novel epimorphic response in mammals that is similar to fingertip regeneration in humans. Both display restricted regenerative capabilities that are amputation-level dependent. Using this endogenous regeneration model in neonatal mice, we have found that noggin treatment inhibits regeneration, thus suggesting a bone morphogenetic protein (BMP) requirement. Using non-regenerating amputation wounds, we show that BMP7 or BMP2 can induce a regenerative response. BMP-induced regeneration involves the formation of a mammalian digit blastema. Unlike the endogenous regeneration response that involves redifferentiation by direct ossification (evolved regeneration), the BMP-induced response involves endochondral ossification (redevelopment). Our evidence suggests that BMP treatment triggers a reprogramming event that re-initiates digit tip development at the amputation wound. These studies demonstrate for the first time that the postnatal mammalian digit has latent regenerative capabilities that can be induced by growth factor treatment.
Yu
Ling
L
Division of Developmental Biology, Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Han
Manjong
M
Yan
Mingquan
M
Lee
Eun-Chee
EC
Lee
Jangwoo
J
Muneoka
Ken
K
D000672:Amputation Stumps / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D001861:Bone Regeneration / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005121:Extremities / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
C525718:BMP2 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D011994:Recombinant Proteins