Using the mouse digit tip to understand human regeneration

There are nearly two million Americans living with a limb amputation due either to illness or traumatic injury.  Even with the best modern surgical intervention, a human limb amputation does not regenerate and results in a fibrotic scar.  Amazingly, however, the amputation of a child’s fingertip does not scar and will completely regenerate all of the missing tissue in the absence of surgical intervention.  The medical implication of understanding the molecular basis of these two dramatically different innate responses is crucial and can potentially lead to therapeutics benefitting millions.

The mouse digit tip, which similarly regenerates upon amputation, is a powerful experimental system and serves as an excellent proxy for human limb regeneration. Upon amputation, the digit tip undergoes epimorphic regeneration, a process involving the proliferation and differentiation of a mass of progenitor cells, termed the blastema, which gives rise to all of the regenerate tissue except the skin.  Understanding how cells are recruited to form a blastema, how they remain proliferative, and how they organize and differentiate into appropriate tissues, are some of the key questions in regenerative biology.  Our lab is focused on determining the molecular pathways and genes necessary for blastema formation, and how they coordinate proliferation and patterning of specialized progenitor cell types during digit tip regeneration.  We are working towards identifying these genes and pathways and learning how to modulate them, with the ultimate goal of inducing regeneration in non-regenerative tissues.