Lef1 is required for progenitor cell identity in the zebrafish lateral line primordium
Lef1 is required for progenitor cell identity in the zebrafish lateral line primordium
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DOI：
10.1242/dev.062554
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发表时间：
2011-09-15
期刊：
影响因子：
4.6
通讯作者：
Nechiporuk, Alexei V.
中科院分区：
文献类型：
--
作者：
McGraw, Hillary F.;Drerup, Catherine M.;Nechiporuk, Alexei V.
斑马鱼后侧线（pLL）是一种感觉系统，由称为神经丘（NM）的机械感觉器官簇组成，这些器官通常沿着躯干表面定位。 NM 由迁移的 pLL 原基沉积，该原基组织成极化玫瑰花结（原始 NM）。在迁移过程中，成熟的原NM从原基的尾部沉积，而前导部分的祖细胞产生新的原NM。 Wnt 信号传导在原基的前导区活跃，整体 Wnt 失活导致原基急剧瓦解和原 NM 形成的丧失。然而，Wnt 通路调节的确切细胞事件尚不清楚。我们鉴定出一种突变株 lef1(nl2)，其 Wnt 效应基因 lef1 中含有一个损伤。 lef1(nl2) 突变体缺乏后部 NM，实时成像显示莲座丛更新在迁移后期失败。令人惊讶的是，通过各种标记的表达测定，lef1(nl2)突变体的整体原基模式似乎没有改变。谱系追踪和嵌合分析表明，主导细胞（假定的祖细胞）移出原基并整合到 NM 中；这导致增殖祖细胞数量减少并最终导致原基解体。我们得出的结论是，Lef1 功能对于初始原基组织或迁移不是必需的，但对于 pLL 形成后期的原 NM 更新是必需的。这些发现揭示了 Wnt 信号通路在斑马鱼机械感觉器官形成过程中的新作用。
The zebrafish posterior lateral line (pLL) is a sensory system that comprises clusters of mechanosensory organs called neuromasts (NMs) that are stereotypically positioned along the surface of the trunk. The NMs are deposited by a migrating pLL primordium, which is organized into polarized rosettes (proto-NMs). During migration, mature proto-NMs are deposited from the trailing part of the primordium, while progenitor cells in the leading part give rise to new proto-NMs. Wnt signaling is active in the leading zone of the primordium and global Wnt inactivation leads to dramatic disorganization of the primordium and a loss of proto-NM formation. However, the exact cellular events that are regulated by the Wnt pathway are not known. We identified a mutant strain, lef1(nl2), that contains a lesion in the Wnt effector gene lef1. lef1(nl2) mutants lack posterior NMs and live imaging reveals that rosette renewal fails during later stages of migration. Surprisingly, the overall primordium patterning, as assayed by the expression of various markers, appears unaltered in lef1(nl2) mutants. Lineage tracing and mosaic analyses revealed that the leading cells (presumptive progenitors) move out of the primordium and are incorporated into NMs; this results in a decrease in the number of proliferating progenitor cells and eventual primordium disorganization. We concluded that Lef1 function is not required for initial primordium organization or migration, but is necessary for proto-NM renewal during later stages of pLL formation. These findings revealed a novel role for the Wnt signaling pathway during mechanosensory organ formation in zebrafish.