Activation of canonical Wnt/-catenin signaling stimulates proliferation in neuromasts in the zebrafish posterior lateral line
Activation of canonical Wnt/-catenin signaling stimulates proliferation in neuromasts in the zebrafish posterior lateral line
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DOI：
10.1002/dvdy.23973
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发表时间：
2013-07-01
影响因子：
2.5
通讯作者：
Meyers, Jason R.
中科院分区：
文献类型：
--
作者：
Head, Jeffery R.;Gacioch, Leah;Meyers, Jason R.
背景资料：斑马鱼的后侧线是从一个迁移的原基发育而来的，原基上沉积了一群细胞，这些细胞沿着躯干以规则的间隔分化成神经瘤。已知这些神经瘤的沉积由控制原基的增殖、迁移和组织的Wnt和FGF信号协调。然而，鲜为人知的是，控制增殖的神经瘤后，他们的沉积。结果如下：我们发现，药理学激活的Wnt/β-catenin信号通路与1-azakenpaullone上调神经瘤后沉积的增殖。这导致神经肥大的大小增加和感觉毛细胞的过度产生。我们还表明，激活Wnt信号返回已经静止的支持细胞在成熟的神经瘤的增殖状态。此外，Wnt信号传导的激活增加了响应毛细胞损伤而返回细胞周期的支持细胞的数量和再生毛细胞的数量。最后，我们发现，抑制Wnt信号dkk 1b过表达抑制增殖过程中的分化和再生。结论：这些数据表明，Wnt/β-连环蛋白信号传导是必要的和足够的发育过程中的侧线祖细胞的增殖控制，神经瘤的持续生长，和毛细胞再生。Developmental Dynamics 242：832-846，2013. (c)2013 Wiley Periodicals，Inc.
Background: The posterior lateral line in zebrafish develops from a migrating primordium that deposits clusters of cells that differentiate into neuromasts at regular intervals along the trunk. The deposition of these neuromasts is known to be coordinated by Wnt and FGF signals that control the proliferation, migration, and organization of the primordium. However, little is known about the control of proliferation in the neuromasts following their deposition. Results: We show that pharmacological activation of the Wnt/-catenin signaling pathway with 1-azakenpaullone upregulates proliferation in neuromasts post-deposition. This results in increased size of the neuromasts and overproduction of sensory hair cells. We also show that activation of Wnt signaling returns already quiescent supporting cells to a proliferative state in mature neuromasts. Additionally, activation of Wnt signaling increases the number of supporting cells that return to the cell cycle in response to hair cell damage and the number of regenerated hair cells. Finally, we show that inhibition of Wnt signaling by overexpression of dkk1b suppresses proliferation during both differentiation and regeneration. Conclusions: These data suggest that Wnt/-catenin signaling is both necessary and sufficient for the control of proliferation of lateral line progenitors during development, ongoing growth of the neuromasts, and hair cell regeneration. Developmental Dynamics 242:832-846, 2013. (c) 2013 Wiley Periodicals, Inc.