Department of Cell, Developmental, and Regenerative Biology, Black Family Stem Cell Institute, The Tisch Cancer Institute, New York City, New York.
Icahn School of Medicine at Mount Sinai, New York City, New York.
Exp Dermatol. 2019 Apr;28(4):374-382. doi: 10.1111/exd.13901. Epub 2019 Mar 13.
Merkel cells are mechanosensory cells involved in tactile discrimination. Merkel cells have been primarily studied in the murine back skin, where they are found in specialized structures called touch domes located around primary hair follicles. Yet, little is known about the morphogenesis of Merkel cells in areas of the skin devoid of hair, such as the glabrous paw skin. Here, we describe Merkel cell formation in the glabrous paw skin during embryogenesis. We first found in the glabrous paw skin that Merkel cells were specified at E15.5, 24 hours later, compared to in the back skin. Additionally, by performing lineage-tracing experiments, we found that unlike in the back skin, SOX9(+) cells do not give rise to Merkel cells in the glabrous paw skin. Finally, we compared the transcriptomes of Merkel cells in the back and the glabrous paw skin and showed that they are similar. Genetic and transcriptome studies showed that the formation of Merkel cells in both regions was controlled by similar regulators. Among them was FGFR2, an upstream factor of MAPK signalling that was reported to have a critical function in Merkel cell formation in the back skin. Here, we showed that FGFR2 is also required for Merkel cell development in the glabrous paw skin. Taken together, our results demonstrate that Merkel cells in the murine back skin and glabrous paw skin are similar, and even though their formation is controlled by a common genetic programme, their precursor cells might differ.
默克尔细胞是参与触觉分辨的机械感觉细胞。默克尔细胞主要在鼠背皮肤中进行研究，在那里它们存在于称为触盘的特殊结构中，位于初级毛囊周围。然而，对于缺乏毛发的皮肤区域（如无毛的爪部皮肤）中的默克尔细胞形态发生，知之甚少。在这里，我们描述了胚胎发生过程中无毛爪部皮肤中的默克尔细胞形成。我们首先在无毛爪部皮肤中发现默克尔细胞在 E15.5 时被指定，比背部皮肤早 24 小时。此外，通过进行谱系追踪实验，我们发现与背部皮肤不同，SOX9(+)细胞在无毛爪部皮肤中不会产生默克尔细胞。最后，我们比较了背部和无毛爪部皮肤中的默克尔细胞的转录组，结果表明它们相似。遗传和转录组研究表明，这两个区域的默克尔细胞形成都受到相似的调节因子的控制。其中包括 FGFR2，它是 MAPK 信号通路的上游因子，据报道，它在背部皮肤中的默克尔细胞形成中具有关键作用。在这里，我们表明 FGFR2 也需要在无毛爪部皮肤中发育默克尔细胞。总之，我们的结果表明，鼠背部皮肤和无毛爪部皮肤中的默克尔细胞相似，尽管它们的形成受到共同遗传程序的控制，但它们的前体细胞可能不同。
