FGF/MAPK/Ets signaling renders pigment cell precursors competent to respond to Wnt signal by directly controlling Ci-Tcf transcription
FGF/MAPK/Ets signaling renders pigment cell precursors competent to respond to Wnt signal by directly controlling Ci-Tcf transcription
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DOI：
10.1242/dev.057323
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发表时间：
2011-04-01
期刊：
影响因子：
4.6
通讯作者：
Spagnuolo, Antonietta
中科院分区：
文献类型：
--
作者：
Squarzoni, Paola;Parveen, Fateema;Spagnuolo, Antonietta
FGF和Wnt通路构成两个基本的信号级联，在几个发育过程中以合作或拮抗的方式出现串扰。在脊椎动物中，这两个级联都参与了色素细胞的发育，但FGF和Wnt之间可能的相互作用仍有待阐明。在本研究中，我们研究了FGF和Wnt信号在C.好吧该物种具有祖先脊索动物的基本特征，因此与脊椎动物共享保守的分子发育机制。化学和有针对性的扰动方法表明，FGF信号，传播的时间从早期原肠胚到神经管关闭，是负责色素细胞前体诱导。该信号通过MAPK途径传递，其激活Ci-Ets 1/2转录因子。靶向干扰经典Wnt通路的下游因子Ci-TCF，表明其对色素细胞分化的贡献。此外，对Ci-Tcf调节区的分析揭示了FGF效应子Ci-Ets 1/2参与色素细胞前体中的Ci-Tcf转录调节。我们的研究结果表明，FGF和经典的Wnt途径都参与了C。色素细胞的诱导和分化。此外，我们提出了一个直接转录调节的情况下，通过MAPK-ERK-Ets 1/2，Wnt下游基因Ci-Tcf的FGF信号级联。在不同的发育过程中已经描述了FGF/Wnt信号串扰的几个例子;然而，据我们所知，在转录水平上的FGF-Wnt交叉相互作用以前从未报道过。这些发现进一步有助于阐明多种FGF-Wnt通路相互作用。
FGF and Wnt pathways constitute two fundamental signaling cascades, which appear to crosstalk in cooperative or antagonistic fashions in several developmental processes. In vertebrates, both cascades are involved in pigment cell development, but the possible interplay between FGF and Wnt remains to be elucidated. In this study, we have investigated the role of FGF and Wnt signaling in development of the pigment cells in the sensory organs of C. intestinalis. This species possesses the basic features of an ancestral chordate, thus sharing conserved molecular developmental mechanisms with vertebrates. Chemical and targeted perturbation approaches revealed that a FGF signal, spreading in time from early gastrulation to neural tube closure, is responsible for pigment cell precursor induction. This signal is transmitted via the MAPK pathway, which activates the Ci-Ets1/2 transcription factor. Targeted perturbation of Ci-TCF, a downstream factor of the canonical Wnt pathway, indicated its contribution to pigment cell differentiation Furthermore, analyses of the Ci-Tcf regulatory region revealed the involvement of the FGF effector, Ci-Ets1/2, in Ci-Tcf transcriptional regulation in pigment cell precursors. Our results indicate that both FGF and the canonical Wnt pathways are involved in C. intestinalis pigment cell induction and differentiation. Moreover, we present a case of direct transcriptional regulation exerted by the FGF signaling cascade, via the MAPK-ERK-Ets1/2, on the Wnt downstream gene Ci-Tcf. Several examples of FGF/Wnt signaling crosstalk have been described in different developmental processes; however, to our knowledge, FGF-Wnt cross-interaction at the transcriptional level has never been previously reported. These findings further contribute to clarifying the multitude of FGF-Wnt pathway interactions.