Live Imaging of Axolotl Digit Regeneration Reveals Spatiotemporal Choreography of Diverse Connective Tissue Progenitor Pools

Abstract

Connective tissues—skeleton, dermis, pericytes, fascia—are a key cell source for regenerating the patterned skeleton during axolotl appendage regeneration. This complexity has made it difficult to identify the cells that regenerate skeletal tissue. Inability to identify these cells has impeded a mechanistic understanding of blastema formation. By tracing cells during digit tip regeneration using brainbow transgenic axolotls, we show that cells from each connective tissue compartment have distinct spatial and temporal profiles of proliferation, migration, and differentiation. Chondrocytes proliferate but do not migrate into the regenerate. In contrast, pericytes proliferate, then migrate into the blastema and give rise solely to pericytes. Periskeletal cells and fibroblasts contribute the bulk of digit blastema cells and acquire diverse fates according to successive waves of migration that choreograph their proximal-distal and tissue contributions. We further show that platelet-derived growth factor signaling is a potent inducer of fibroblast migration, which is required to form the blastema.Fil: Currie, Joshua D.. Technische Universität Dresden; Alemania. Max Planck Institute of Molecular Cell Biology and Genetics; AlemaniaFil: Kawaguchi, Akane. Technische Universität Dresden; AlemaniaFil: Traspas, Ricardo Moreno. Technische Universität Dresden; AlemaniaFil: Schuez, Maritta. Technische Universität Dresden; AlemaniaFil: Chara, Osvaldo. Technische Universität Dresden; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; ArgentinaFil: Tanaka, Elly M.. Technische Universität Dresden; Alemania. Max Planck Institute of Molecular Cell Biology and Genetics; Alemani