Twist1 contributes to cranial bone initiation and dermal condensation by maintaining Wnt signaling responsiveness.
Twist1 contributes to cranial bone initiation and dermal condensation by maintaining Wnt signaling responsiveness.
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DOI：
10.1002/dvdy.24367
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Atit RP
中科院分区：
文献类型：
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作者：
Goodnough LH;Dinuoscio GJ;Atit RP
眶上弓间质中颅骨和真皮成纤维细胞祖细胞的特异性依赖于Wnt/β-catenin信号。这些细胞如何解释有指导意义的信号信号并分化成这两种谱系的机制尚不清楚。Twist1是Wnt/β-catenin信号通路的靶点，在颅骨和真皮谱系中表达。在这里，我们发现小鼠颅间质中Twist1表达的开始依赖于外胚层wnt和间充质β-catenin活性。眶上弓间质Twist1的条件缺失导致颅骨发育不全和真皮发育不良，以及眼和腭颅面畸形。Twist1通过维持Wnt的响应性而优先需要颅骨谱系的承诺。在有条件缺乏Twist1的情况下，颅真皮不能凝结和顶部扩张，导致广泛的颅真皮发育不全，毛囊很少且未分化。因此，Twist1作为典型Wnt/β-catenin信号传导的靶标，也具有维持Wnt反应性的功能，并且是颅骨命运选择和皮肤凝结的关键效应因子。
Specification of cranial bone and dermal fibroblast progenitors in the supraorbital arch mesenchyme is Wnt/β-catenin signaling-dependent. The mechanism underlying how these cells interpret instructive signaling cues and differentiate into these two lineages is unclear. Twist1 is a target of the Wnt/β-catenin signaling pathway and is expressed in cranial bone and dermal lineages. Here, we show that onset of Twist1 expression in the mouse cranial mesenchyme is dependent on ectodermal Wnts and mesenchymal β-catenin activity. Conditional deletion of Twist1 in the supraorbital arch mesenchyme leads to cranial bone agenesis and hypoplastic dermis, as well as craniofacial malformation of eyes and palate. Twist1 is preferentially required for cranial bone lineage commitment by maintaining Wnt responsiveness. In the conditional absence of Twist1, the cranial dermis fails to condense and expand apically leading to extensive cranial dermal hypoplasia with few and undifferentiated hair follicles. Thus, Twist1, a target of canonical Wnt/β-catenin signaling, also functions to maintain Wnt responsiveness and is a key effector for cranial bone fate selection and dermal condensation.