A transitional extracellular matrix instructs cell behavior during muscle regeneration.
Urodele amphibians regenerate appendages through the recruitment of progenitor cells into a blastema that rebuilds the lost tissue. Blastemal formation is accompanied by extensive remodeling of the extracellular matrix. Although this remodeling process is important for appendage regeneration, it is not known whether the remodeled matrix directly influences the generation and behavior of blastemal progenitor cells. By integrating in vivo 3-dimensional spatiotemporal matrix maps with in vitro functional time-lapse imaging, we show that key components of this dynamic matrix, hyaluronic acid, tenascin-C and fibronectin, differentially direct cellular behaviors including DNA synthesis, migration, myotube fragmentation and myoblast fusion. These data indicate that both satellite cells and fragmenting myofibers contribute to the regeneration blastema and that the local extracellular environment provides instructive cues for the regenerative process. The fact that amphibian and mammalian myoblasts exhibit similar responses to various matrices suggests that the ability to sense and respond to regenerative signals is evolutionarily conserved.
Calve
Sarah
S
Department of Pediatrics, Northwestern University, The Feinberg School of Medicine, Children's Memorial Research Center, 2300 Children's Plaza, Chicago, IL 60614, USA. s-calve@northwestern.edu
Odelberg
Shannon J
SJ
Simon
Hans-Georg
HG
D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology*; D005121:Extremities; D021621:Imaging, Three-Dimensional; D008954:Models, Biological; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology; D009132:Muscles / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012038:Regeneration / Q000502:physiology*; D012455:Salamandridae; D013234:Stem Cells / Q000166:cytology