Section of Molecular, Cell and Developmental Biology, Institute of Cellular and Molecular Biology, University of Texas at Austin, USA.
Dev Biol. 2012 Sep 1;369(1):65-75. doi: 10.1016/j.ydbio.2012.05.032. Epub 2012 Jun 16.
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.
颅面骨骼的正常功能需要许多单个骨骼元素的正确塑形。神经嵴细胞产生了大部分的颅面骨骼,骨骼元素的形态发生发生在短暂的、反复出现的称为咽弓的结构中。单个元素的形状取决于神经嵴中的内在模式以及来自弓内相邻组织的神经嵴的外在信号。已知 Hedgehog (Hh) 信号在颅面发育中发挥作用,但它在颅面骨骼的内在和外在模式形成中的作用仍未得到很好的理解。在这里,我们表明咽弓的形态发生运动和神经嵴的模式形成需要 Hh 信号。Hh 信号的缺失(在 smoothened (smo) 突变体中)破坏了一些 Dlx 基因的表达以及神经嵴背/腹模式形成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 信号以进行正确的模式形成。尽管进行了挽救,但面部骨骼的形态发生并未完全恢复。通过移植分析,我们发现 Hh 信号还需要另外两个要求。内胚层需要接收 Hh 信号才能使咽弓的形态发生运动正常,而神经嵴需要接收 Hh 信号才能维持 sonic hedgehog 在内胚层中的表达的反向信号的活性。总的来说,这些结果表明 Hh 信号对于建立颅面骨骼的内在和外在模式形成信息是必不可少的。