Tissue-specific analysis of Fgf18 gene function in palate development.

Tissue-specific analysis of Fgf18 gene function in palate development.
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DOI:
10.1002/dvdy.259
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发表时间:
2021-04
期刊:
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子:
--
通讯作者:
Jiang R
Jiang R
中科院分区:
其他
文献类型:
--
作者:
Yue M;Lan Y;Liu H;Wu Z;Imamura T;Jiang R

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先前的研究表明,缺乏成纤维细胞生长因子18(Fgf18)功能的小鼠存在腭裂缺陷,并且FGF18基因位点与人类的唇腭裂相关,但Fgf18在腭形成过程中所起的具体作用尚不清楚。 我们发现,在小鼠胚胎腭突生长和融合过程中,Fgf18在发育中的腭板、下颌骨和舌头中呈现区域受限性表达。在神经嵴衍生的颅面间充质中,Fgf18的组织特异性失活导致Fgf18c/c;Wnt1 - Cre突变小鼠的下颌骨缩短以及额骨、鼻骨和前颅底骨骼成分的骨化减少。约64%的Fgf18c/c;Wnt1 - Cre小鼠出现腭裂。尽管许多Fgf18c/c;Wnt1 - Cre胚胎的腭板抬高受损,但在Fgf18c/c;Wnt1 - Cre胚胎与其同窝对照小鼠之间,未检测到腭细胞增殖有显著差异。来自Fgf18c/c;Wnt1 - Cre胚胎的胚胎上颌外植体在器官培养中显示出与对照胚胎的上颌外植体相似的成功的腭板抬高和融合。此外,在早期腭间充质中Fgf18的组织特异性失活并未导致腭裂。 这些结果表明,Fgf18在神经嵴衍生的间充质中的表达对下颌骨和多种颅面骨的发育起着关键作用,但Fgf18在腭间充质中的表达对腭形成是可有可无的。
Previous studies showed that mice lacking Fgf18 function had cleft palate defects and that the FGF18 locus was associated with cleft lip and palate in humans, but what specific roles Fgf18 plays during palatogenesis are unclear. We show that Fgf18 exhibits regionally restricted expression in developing palatal shelves, mandible, and tongue, during palatal outgrowth and fusion in mouse embryos. Tissue-specific inactivation of Fgf18 throughout neural crest-derived craniofacial mesenchyme caused shortened mandible and reduction in ossification of the frontal, nasal, and anterior cranial base skeletal elements in Fgf18c/c;Wnt1-Cre mutant mice. About 64% of Fgf18c/c;Wnt1-Cre mice exhibited cleft palate. Whereas palatal shelf elevation was impaired in many Fgf18c/c;Wnt1-Cre embryos, no significant difference in palatal cell proliferation was detected between Fgf18c/c;Wnt1-Cre embryos and their control littermates. Embryonic maxillary explants from Fgf18c/c;Wnt1-Cre embryos showed successful palatal shelf elevation and fusion in organ culture similar to the maxillary explants from control embryos. Furthermore, tissue-specific inactivation of Fgf18 in the early palatal mesenchyme did not cause cleft palate. These results demonstrate a critical role for Fgf18 expression in the neural crest-derived mesenchyme for the development of the mandible and multiple craniofacial bones but Fgf18 expression in the palatal mesenchyme is dispensable for palatogenesis.
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发表时间: 2016-02
期刊: Developmental dynamics : an official publication of the American Association of Anatomists
影响因子: --
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