Xenopus Dusp6 modulates FGF signaling to precisely pattern pre-placodal ectoderm
Xenopus Dusp6 modulates FGF signaling to precisely pattern pre-placodal ectoderm
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DOI：
10.1016/j.ydbio.2022.05.009
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发表时间：
2022-05-24
影响因子：
2.7
通讯作者：
Michiue，Tatsuo
中科院分区：
文献类型：
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作者：
Tsukano，Kohei;Yamamoto，Takayoshi;Michiue，Tatsuo
前基板外胚层（PPE），在脊椎动物早期发育过程中形成的马蹄形狭窄区域，产生多种类型的感觉器官和神经节。对于PPE诱导，需要一定水平的FGF信号激活。然而，难以在个体之间可重复地诱导具有基因表达变化的狭窄区域，包括FGF。FGF信号传导的细胞内调节因子Dusp 6通过FGF信号激活表达，并在成人组织中使下游调节因子ERK 1/2失活;然而，其在早期发育中的作用尚不清楚。在这里，我们揭示了Dusp 6在XenopusPPE中以FGF依赖的方式表达。获得和丧失功能的实验表明，Dusp 6是PPE基因Six 1的表达以及相邻区域、神经板和神经嵴的图案化所必需的。为了揭示Dusp 6在可变FGF产生中的重要性，我们用FGF珠植入进行Dusp 6敲低，这导致了不同的Six 1表达模式。总之，这些结果表明Dusp 6是PPE形成所需的，并且它通过介导FGF信号传导而有助于PPE的稳健模式化。
Pre-placodal ectoderm (PPE), a horseshoe-shaped narrow region formed during early vertebrate development, gives rise to multiple types of sensory organs and ganglia. For PPE induction, a certain level of FGF signal activation is required. However, it is difficult to reproducibly induce the narrow region with variations in gene expression, including FGF, among individuals. An intracellular regulatory factor of FGF signaling, Dusp6, is expressed by FGF signal activation and inactivates a downstream regulator, ERK1/2, in adult tissues; however, its role in early development is not well known. Here, we reveal thatDusp6is expressed in an FGF-dependent manner inXenopusPPE. Gain- and loss-of-function experiments showed thatDusp6is required for expression of a PPE gene,Six1, and patterning of adjacent regions, neural plate, and neural crest. To reveal the importance of Dusp6 in variable FGF production, we performedDusp6knockdown with FGF-bead implantation, which resulted in varyingSix1expression patterns. Taken together, these results suggest that Dusp6 is required for PPE formation and that it contributes to the robust patterning of PPE by mediating FGF signaling.