En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration.

En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration.
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DOI:
10.1016/j.celrep.2022.111701
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发表时间:
2022-11-22
期刊:
影响因子:
8.8
通讯作者:
--
中科院分区:
生物学1区
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--
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小鼠的指尖在截肢后会再生。再生的模式是如何形成的尚不清楚,但一个长期存在的假设提出,发育模式机制在再生过程中被重复使用。指尖骨表现出背腹 (DV) 极性,因此我们重点关注 En1 和 Lmx1b,这是肢体发育过程中 DV 模式所必需的两个因素。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 分别在再生指尖上皮和间充质中表达,但没有 DV 极性。指尖骨形态的条件遗传学和定量分析确定,成人指尖再生中 En1 或 Lmx1b 的遗传缺失会适度减少骨再生,但不影响 DV 模式。总的来说,我们的数据表明,虽然 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定义 DV 轴。约翰逊等人。发现背腹 (DV) 基因 En1 和 Lmx1b 在再生小鼠指尖中表达,但没有 DV 极性。条件遗传学和骨形态分析表明 En1 或 Lmx1b 不会改变再生的数字 DV 模式,驳斥了胚胎肢体模式通路在再生过程中被重复使用的假设。
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. Johnson et al. find dorsal-ventral (DV) genes En1 and Lmx1b are expressed in regenerating mouse digit tips, but without DV polarity. Conditional genetics and bone morphology analyses indicate En1 or Lmx1b do not alter regenerated digit DV patterning, refuting the hypothesis that embryonic limb patterning pathways are re-used during regeneration.
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