Digit specific denervation does not inhibit mouse digit tip regeneration.

Digit specific denervation does not inhibit mouse digit tip regeneration.
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DOI:
10.1016/j.ydbio.2022.03.007
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发表时间:
2022-06
影响因子:
2.7
通讯作者:
Muneoka, Ken
Muneoka, Ken
中科院分区:
生物学3区
文献类型:
--
作者:
Dolan, Connor P.;Imholt, Felisha;Yan, Mingquan;Yang, Tae-Jung;Gregory, Joshua;Qureshi, Osama;Zimmel, Katherine;Sherman, Kirby M.;Smith, Hannah M.;Falck, Alyssa;Leininger, Eric;Yu, Ling;Brunauer, Regina;Suva, Larry J.;Gaddy, Dana;Dawson, Lindsay A.;Muneoka, Ken

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长期以来,鱼类和两栖动物的胚泡形成和附属物的表型再生都需要神经营养因子的神经依赖产生。再生的小鼠指尖和人类指尖是哺乳动物的表型再生模型,而小鼠的肢体失神经会抑制这种反应。陆生脊椎动物肢体失神经研究的一个复杂问题是,实验模型也会导致严重的瘫痪,从而损害附件的使用,并降低失神经组织的机械负荷。因此,目前尚不清楚肢体失神经是否通过神经营养信号的丧失或机械负荷的丧失而损害再生,或两者兼而有之。在此,我们开发了一种新的外科手术方法,在不损害行走和机械负荷的情况下,对单个手指进行特定的去神经。我们证明,指端特异性神经支配不会抑制而是减弱指尖再生,部分原因是伤口愈合延迟。然而,用促进闭合的创面敷料治疗失神经的手指,可以部分挽救再生反应。与目前对哺乳动物表型再生的理解相反,这些研究表明,小鼠的指尖再生不依赖于周围神经,这一观察结果应该有助于继续采用哺乳动物再生医学的方法。
It is long-established that innervation-dependent production of neurotrophic factors is required for blastema formation and epimorphic regeneration of appendages in fish and amphibians. The regenerating mouse digit tip and the human fingertip are mammalian models for epimorphic regeneration, and limb denervation in mice inhibits this response. A complicating issue of limb denervation studies in terrestrial vertebrates is that the experimental models also cause severe paralysis therefore impairing appendage use and diminishing mechanical loading of the denervated tissues. Thus, it is unclear whether the limb denervation impairs regeneration via loss of neurotrophic signaling or loss of mechanical load, or both. Herein, we developed a novel surgical procedure in which individual digits were specifically denervated without impairing ambulation and mechanical loading. We demonstrate that digit specific denervation does not inhibit but attenuates digit tip regeneration, in part due to a delay in wound healing. However, treating denervated digits with a wound dressing that enhances closure results in a partial rescue of the regeneration response. Contrary to the current understanding of mammalian epimorphic regeneration, these studies demonstrate that mouse digit tip regeneration is not peripheral nerve dependent, an observation that should inform continued mammalian regenerative medicine approaches.
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