Dolan Connor P, Yan Mingquan, Zimmel Katherine, Yang Tae-Jung, Leininger Eric, Dawson Lindsay A, Muneoka Ken
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
Department of Cell and Molecular Biology, School of Science and Engineering, Tulane University, New Orleans, LA 70118, USA.
Dev Biol. 2019 Jan 15;445(2):237-244. doi: 10.1016/j.ydbio.2018.11.010. Epub 2018 Nov 17.
Mice are intrinsically capable of regenerating the tips of their digits after amputation. Mouse digit tip regeneration is reported to be a peripheral nerve-dependent event. However, it is presently unknown what types of nerves and Schwann cells innervate the digit tip, and to what extent these cells regenerate in association with the regenerative response. Given the necessity of peripheral nerves for mammalian regeneration, we investigated the neuroanatomy of the unamputated, regenerating, and regenerated mouse digit tip. Using immunohistochemistry for β-III-tubulin (β3T) or neurofilament H (NFH), substance P (SP), tyrosine hydroxylase (TH), myelin protein zero (P0), and glial fibrillary acidic protein (GFAP), we identified peripheral nerve axons (sensory and sympathetic), and myelinating- and non-myelinating-Schwann cells. Our findings show that the digit tip is innervated by two digital nerves that each bifurcate into a bone marrow (BM) and connective tissue (CT) branch. The BM branches are composed of sympathetic axons that are ensheathed by non-myelinating-Schwann cells whereas the CT branches are composed of sensory and sympathetic axons and are ensheathed by myelinating- and non-myelinating-Schwann cells. The regenerated digit neuroanatomy differs from unamputated digit in several key ways. First, there is 7.5 fold decrease in CT branch axons in the regenerated digit compared to the unampuated digit. Second, there is a 5.6 fold decrease in myelinating-Schwann cells in the regenerated digit compared to the unamputated digit that is consistent with the decrease in CT branch axons. Importantly, we also find that the central portion of the regenerating digit blastema is aneural, with axons and Schwann cells restricted to peripheral and distal blastema regions. Finally, we show that even with impaired innervation, digits maintain the ability to regenerate after re-amputation. Taken together, these data indicate that nerve regeneration is impaired in the context of mouse digit tip regeneration.
小鼠在截肢后本质上能够再生其指尖。据报道，小鼠指尖再生是一个依赖于周围神经的过程。然而，目前尚不清楚何种类型的神经和施万细胞支配指尖，以及这些细胞在再生反应中再生的程度如何。鉴于周围神经对哺乳动物再生的必要性，我们研究了未截肢、正在再生和已再生的小鼠指尖的神经解剖结构。通过使用针对β-III-微管蛋白（β3T）或神经丝H（NFH）、P物质（SP）、酪氨酸羟化酶（TH）、髓磷脂蛋白零（P0）和胶质纤维酸性蛋白（GFAP）的免疫组织化学方法，我们识别出了周围神经轴突（感觉和交感神经）以及有髓鞘和无髓鞘的施万细胞。我们的研究结果表明，指尖由两条指神经支配，每条指神经都分叉为骨髓（BM）和结缔组织（CT）分支。BM分支由被无髓鞘施万细胞包裹的交感神经轴突组成，而CT分支由感觉和交感神经轴突组成，并被有髓鞘和无髓鞘的施万细胞包裹。再生指尖的神经解剖结构在几个关键方面与未截肢的指尖不同。首先，与未截肢的指尖相比，再生指尖中CT分支轴突减少了7.5倍。其次，与未截肢的指尖相比，再生指尖中有髓鞘施万细胞减少了5.6倍，这与CT分支轴突的减少一致。重要的是，我们还发现正在再生的指尖芽基的中央部分无神经，轴突和施万细胞仅限于外周和远端芽基区域。最后，我们表明，即使神经支配受损，指尖在再次截肢后仍保持再生能力。综上所述，这些数据表明在小鼠指尖再生的情况下神经再生受损。
