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Development 137 (4): 551-559

DEVELOPMENT AND STEM CELLS

BMP signaling induces digit regeneration in neonatal mice

Ling Yu1,*, Manjong Han1,*, Mingquan Yan1, Eun-Chee Lee1, Jangwoo Lee1, and Ken Muneoka1,2,{dagger}

1 Division of Developmental Biology, Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
2 Center for Bioenvironmental Research, Tulane University, New Orleans, LA 70118, USA.

{dagger} Author for correspondence (kmuneoka{at}tulane.edu)

Accepted for publication 8 December 2009.

Abstract: 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.

Key Words: BMP7 • BMP2 • Digit • Regeneration • Blastema • Endochondral ossification • Mouse

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Advanced BMP Gene Therapies for Temporal and Spatial Control of Bone Regeneration.
C. G. Wilson, F. M. Martin-Saavedra, N. Vilaboa, and R. T. Franceschi (2013)
Journal of Dental Research 92, 409-417
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