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Wnt信号通路在体内黑素细胞分化过程中持续发挥作用。

An ongoing role for Wnt signaling in differentiating melanocytes in vivo.

作者信息

Vibert Laura, Aquino Gerardo, Gehring Ines, Subkankulova Tatiana, Schilling Thomas F, Rocco Andrea, Kelsh Robert N

机构信息

Developmental Biology Programme, Department of Biology and Biochemistry, Centre for Regenerative Medicine, University of Bath, Bath, UK.

Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.

出版信息

Pigment Cell Melanoma Res. 2017 Mar;30(2):219-232. doi: 10.1111/pcmr.12568. Epub 2017 Mar 9.

DOI:10.1111/pcmr.12568
PMID:27977907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5360516/
Abstract

A role for Wnt signaling in melanocyte specification from neural crest is conserved across vertebrates, but possible ongoing roles in melanocyte differentiation have received little attention. Using a systems biology approach to investigate the gene regulatory network underlying stable melanocyte differentiation in zebrafish highlighted a requirement for a positive-feedback loop involving the melanocyte master regulator Mitfa. Here, we test the hypothesis that Wnt signaling contributes to that positive feedback. We show firstly that Wnt signaling remains active in differentiating melanocytes and secondly that enhanced Wnt signaling drives elevated transcription of mitfa. We show that chemical activation of the Wnt signaling pathway at early stages of melanocyte development enhances melanocyte specification as expected, but importantly that at later (differentiation) stages, it results in altered melanocyte morphology, although melanisation is not obviously affected. Downregulation of Wnt signaling also results in altered melanocyte morphology and organization. We conclude that Wnt signaling plays a role in regulating ongoing aspects of melanocyte differentiation in zebrafish.

摘要

Wnt信号通路在神经嵴来源的黑素细胞特化过程中的作用在脊椎动物中是保守的，但在黑素细胞分化过程中可能持续发挥的作用却很少受到关注。利用系统生物学方法研究斑马鱼中稳定黑素细胞分化背后的基因调控网络，突出了一个涉及黑素细胞主调控因子Mitfa的正反馈环的必要性。在此，我们检验Wnt信号通路促成该正反馈的假说。我们首先表明Wnt信号通路在分化中的黑素细胞中保持活跃，其次表明增强的Wnt信号通路驱动mitfa转录升高。我们表明，在黑素细胞发育早期阶段对Wnt信号通路进行化学激活，如预期那样增强了黑素细胞特化，但重要的是，在后期（分化）阶段，尽管黑素化没有明显受到影响，但它导致黑素细胞形态改变。Wnt信号通路的下调也会导致黑素细胞形态和组织的改变。我们得出结论，Wnt信号通路在调节斑马鱼黑素细胞分化的持续过程中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/72f180afd9e2/PCMR-30-219-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/0b3fd45cf68d/PCMR-30-219-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/dda66d7e2b57/PCMR-30-219-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/9261255b72cf/PCMR-30-219-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/2556d067fec9/PCMR-30-219-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/72f180afd9e2/PCMR-30-219-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/0b3fd45cf68d/PCMR-30-219-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/dda66d7e2b57/PCMR-30-219-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/9261255b72cf/PCMR-30-219-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/2556d067fec9/PCMR-30-219-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3524/5396377/72f180afd9e2/PCMR-30-219-g005.jpg

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