We report that during mouse fetal development transcripts of Msx1 and Msx2 become progressively restricted to cells that will form more distal digit structures; the Msx2 expression domain is always more distal than Msx1. At birth both Msx1 and Msx2 are expressed in cells of the nail bed and hair follicle. We have found that the regenerative ability of mouse digit tips is restricted to levels in which the amputation plane is within the region of Msx1, but not Msx2, expression in early fetal digits and to levels where both Msx1 and Msx2 are expressed in late fetal and neonatal digits. Fetal digit tip regeneration is rapid and completed by birth, whereas neonatal digit tip regeneration requires 4 weeks and is sometimes imperfect. In both fetal and neonatal digits, we find that both Msx1 and Msx2 are expressed during regeneration, but not during wound healing associated with proximal amputations where no regenerative response is observed. These data support the hypothesis that the expression of Msx genes are important for digit cells to initiate and participate in a regenerative response.

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