Fgf10mutant newts can regenerate normal limbs despite severe developmental hindlimb defects

Abstract

AbstractIn the amniote limb, FGF10 is essential for limb bud initiation and outgrowth. However, whether this function is broadly conserved in tetrapods and/or involved in adult limb regeneration remains unknown. To tackle this question, we established anFgf10null mutant line in the newtPleurodeles waltlwhich have amazing regenerative ability. WhileFgf10mutant forelimbs develop normally, the hindlimbs exhibit severe digit reduction, fail to ossify the zeugopod, and downregulate FGF target genes likeSall1, Runx1andHoxa11/d11. Despite these developmental defects,Fgf10mutants were able to regenerate near-normal hindlimbs. Together, our results suggest an important role forFgf10in hindlimb digit formation and zeugopod ossification during development, but little or no function in regeneration, suggesting that different mechanisms operate during limb regeneration versus development.