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皮肤附属物依赖的斑马鱼 Merkel 细胞模式形成。

Dermal appendage-dependent patterning of zebrafish Merkel cells.

机构信息

Department of Biology, University of Washington, Seattle, United States.

Molecular and Cellular Biology Program, University of Washington, Seattle, United States.

出版信息

Elife. 2023 Jan 17;12:e85800. doi: 10.7554/eLife.85800.

Abstract

Touch system function requires precise interactions between specialized skin cells and somatosensory axons, as exemplified by the vertebrate mechanosensory Merkel cell-neurite complex. Development and patterning of Merkel cells and associated neurites during skin organogenesis remain poorly understood, partly due to the in utero development of mammalian embryos. Here, we discover Merkel cells in the zebrafish epidermis and identify Atonal homolog 1a (Atoh1a) as a marker of zebrafish Merkel cells. We show that zebrafish Merkel cells derive from basal keratinocytes, express neurosecretory and mechanosensory machinery, extend actin-rich microvilli, and complex with somatosensory axons, all hallmarks of mammalian Merkel cells. Merkel cells populate all major adult skin compartments, with region-specific densities and distribution patterns. In vivo photoconversion reveals that Merkel cells undergo steady loss and replenishment during skin homeostasis. Merkel cells develop concomitant with dermal appendages along the trunk and loss of Ectodysplasin signaling, which prevents dermal appendage formation, reduces Merkel cell density by affecting cell differentiation. By contrast, altering dermal appendage morphology changes the distribution, but not density, of Merkel cells. Overall, our studies provide insights into touch system maturation during skin organogenesis and establish zebrafish as an experimentally accessible in vivo model for the study of Merkel cell biology.

摘要

触觉系统功能需要专门的皮肤细胞和躯体感觉轴突之间的精确相互作用,脊椎动物机械感觉 Merkel 细胞-神经纤维复合物就是一个很好的例子。皮肤器官发生过程中 Merkel 细胞和相关神经纤维的发育和模式形成仍知之甚少,部分原因是哺乳动物胚胎的体内发育。在这里,我们在斑马鱼表皮中发现了 Merkel 细胞,并确定 Atonal 同源物 1a(Atoh1a)是斑马鱼 Merkel 细胞的标志物。我们表明,斑马鱼 Merkel 细胞来源于基底角质形成细胞,表达神经分泌和机械感觉机制,延伸富含肌动蛋白的微绒毛,并与躯体感觉轴突复合,所有这些都是哺乳动物 Merkel 细胞的特征。Merkel 细胞遍布所有主要的成年皮肤区室,具有特定区域的密度和分布模式。体内光转化显示,Merkel 细胞在皮肤稳态过程中经历稳定的丧失和补充。Merkel 细胞与沿躯干的真皮附属物同时发育,并且 Ectodysplasin 信号丢失,这阻止了真皮附属物的形成,通过影响细胞分化,降低 Merkel 细胞的密度。相比之下,改变真皮附属物的形态会改变 Merkel 细胞的分布,但不会改变密度。总体而言,我们的研究为皮肤器官发生过程中触觉系统成熟提供了深入的了解,并确立了斑马鱼作为研究 Merkel 细胞生物学的可在体内进行实验的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6213/9901935/95257bd50c6c/elife-85800-fig1.jpg

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