Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
Cell Rep. 2022 Nov 22;41(8):111701. doi: 10.1016/j.celrep.2022.111701.
The mouse digit tip regenerates following amputation. How the regenerate is patterned is unknown, but a long-standing hypothesis proposes developmental patterning mechanisms are re-used during regeneration. The digit tip bone exhibits dorsal-ventral (DV) polarity, so we focus on En1 and Lmx1b, two factors necessary for DV patterning during limb development. We investigate whether they are re-expressed during regeneration in a developmental-like pattern and whether they direct DV morphology of the regenerate. We find that both En1 and Lmx1b are expressed in the regenerating digit tip epithelium and mesenchyme, respectively, but without DV polarity. Conditional genetics and quantitative analysis of digit tip bone morphology determine that genetic deletion of En1 or Lmx1b in adult digit tip regeneration modestly reduces bone regeneration but does not affect DV patterning. Collectively, our data suggest that, while En1 and Lmx1b are re-expressed during mouse digit tip regeneration, they do not define the DV axis during regeneration.
鼠标指尖在截肢后会再生。目前尚不清楚再生是如何形成模式的,但一个长期存在的假设提出,在再生过程中会重新利用发育模式形成机制。指尖骨表现出背腹(DV)极性,因此我们专注于 En1 和 Lmx1b,这两个因子在肢体发育过程中对于 DV 模式形成是必需的。我们研究它们是否在再生过程中以类似发育的模式重新表达,以及它们是否指导再生的 DV 形态。我们发现,En1 和 Lmx1b 分别在再生的指尖上皮和间充质中表达,但没有 DV 极性。对指尖骨形态的条件遗传学和定量分析确定,成年指尖再生中 En1 或 Lmx1b 的基因缺失适度减少了骨再生,但不影响 DV 模式形成。总的来说,我们的数据表明,尽管 En1 和 Lmx1b 在小鼠指尖再生过程中重新表达,但它们在再生过程中并不确定 DV 轴。
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