Hh signaling regulates patterning and morphogenesis of the pharyngeal arch-derived skeleton.
Hh signaling regulates patterning and morphogenesis of the pharyngeal arch-derived skeleton.
复制标题
Hh 信号传导调节咽弓衍生骨骼的模式和形态发生。
DOI：
10.1016/j.ydbio.2012.05.032
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发表时间：
2012
影响因子：
2.7
通讯作者：
Eberhart,JohannK
中科院分区：
文献类型：
--
作者：
Swartz,MaryE;Nguyen,Van;McCarthy,NeilQ;Eberhart,JohannK
颅面骨骼的正常功能需要许多个体骨骼元素的正确成形。神经嵴细胞产生大部分的颅面骨骼和骨骼元素的形态发生在短暂的，重复的结构称为咽弓。单个元素的形状取决于神经嵴内的内在图案以及来自弓内相邻组织的神经嵴的外在信号。刺猬（Hh）信号是已知的颅面发育中发挥作用，但其参与颅面骨骼的内在和外在模式仍然没有得到很好的理解。在这里，我们表明，形态发生运动的咽弓和图案的神经嵴需要Hh信号。在smoothened（smo）突变体中，Hh信号传导的丢失破坏了一些Dlx基因以及神经嵴背侧/腹侧图案的其他标志物的表达。将野生型神经嵴细胞移植到smo突变体中可以挽救这种缺陷，表明神经嵴需要接收Hh信号以进行适当的图案化。尽管抢救，面部骨骼的形态发生并没有完全恢复。通过移植分析，我们发现Hh信令的两个额外要求。内胚层需要Hh信号的接收以用于咽弓的适当形态发生运动，并且神经嵴需要Hh信号的接收以用于维持内胚层中的音刺猬表达的反向信号的活性。总的来说，这些结果表明，Hh信号是必不可少的，以建立内在和外在的颅面骨骼图案信息。
The proper function of the craniofacial skeleton requires the proper shaping of many individual skeletal elements. Neural crest cells generate much of the craniofacial skeleton and morphogenesis of skeletal elements occurs in transient, reiterated structures termed pharyngeal arches. The shape of individual elements depends upon intrinsic patterning within the neural crest as well as extrinsic signals to the neural crest from adjacent tissues within the arches. Hedgehog (Hh) signaling is known to play roles in craniofacial development, yet its involvement in intrinsic and extrinsic patterning of the craniofacial skeleton is still not well understood. Here, we show that morphogenetic movements of the pharyngeal arches and patterning of the neural crest require Hh signaling. Loss of Hh signaling, in smoothened (smo) mutants, disrupts the expression of some Dlx genes as well as other markers of dorsal/ventral patterning of the neural crest. Transplantation of wild-type neural crest cells into smo mutants rescues this defect, demonstrating that the neural crest requires reception of Hh signals for proper patterning. Despite the rescue, morphogenesis of the facial skeleton is not fully recovered. Through transplant analyses, we find two additional requirements for Hh signaling. The endoderm requires the reception of Hh signals for proper morphogenetic movements of the pharyngeal arches and the neural crest require the reception of Hh signaling for the activity of a reverse signal that maintains sonic hedgehog expression in the endoderm. Collectively, these results demonstrate that Hh signaling is essential to establish intrinsic and extrinsic patterning information for the craniofacial skeleton.