Bryant Donald M, Sousounis Konstantinos, Farkas Johanna E, Bryant Sevara, Thao Neng, Guzikowski Anna R, Monaghan James R, Levin Michael, Whited Jessica L
Harvard Medical School, the Harvard stem Cell Institute, and the Department of Orthopedic Surgery, Brigham & Women's Hospital, Cambridge, MA 02139, USA.
Harvard Medical School, the Harvard stem Cell Institute, and the Department of Orthopedic Surgery, Brigham & Women's Hospital, Cambridge, MA 02139, USA; Allen Discovery Center at Tufts, Medford, MA 02155, USA.
Dev Biol. 2017 Apr 1;424(1):1-9. doi: 10.1016/j.ydbio.2017.02.013. Epub 2017 Feb 21.
Matching appendage size to body size is fundamental to animal function. Generating an appropriately-sized appendage is a robust process executed during development which is also critical for regeneration. When challenged, larger animals are programmed to regenerate larger limbs than smaller animals within a single species. Understanding this process has important implications for regenerative medicine. To approach this complex question, models with altered appendage size:body size ratios are required. We hypothesized that repeatedly challenging axolotls to regrow limb buds would affect their developmental program resulting in altered target morphology. We discovered that after 10 months following this experimental procedure, limbs that developed were permanently miniaturized. This altered target morphology was preserved upon amputation and regeneration. Future experiments using this platform should provide critical information about how target limb size is encoded within limb progenitors.
使附肢大小与身体大小相匹配是动物功能的基础。生成大小合适的附肢是在发育过程中执行的一个稳健过程，这对再生也至关重要。当受到挑战时，同一物种内较大的动物被设定为比小的动物再生出更大的肢体。了解这个过程对再生医学具有重要意义。为了解决这个复杂的问题，需要附肢大小与身体大小比例改变的模型。我们假设反复挑战蝾螈使其再生肢芽会影响其发育程序，从而导致目标形态改变。我们发现，在这个实验过程进行10个月后，发育出的肢体永久变小。这种改变的目标形态在截肢和再生后得以保留。使用这个平台的未来实验应该能提供有关肢体祖细胞如何编码目标肢体大小的关键信息。
