Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation.
Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation.
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DOI：
10.1016/j.ydbio.2010.12.028
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发表时间：
2011-02-15
影响因子：
2.7
通讯作者：
Jiang R
中科院分区：
文献类型：
--
作者：
Baek JA;Lan Y;Liu H;Maltby KM;Mishina Y;Jiang R
腭裂，包括粘膜下腭裂，是人类最常见的出生缺陷之一。显性腭裂是由发育中的腭架的生长或融合缺陷引起的，而粘膜下性腭裂是以腭骨的缺陷为特征的。在这篇报道中，我们发现编码骨形态发生蛋白(BMP)I型受体的BMPR1A基因在腭部发育过程中优先在初级腭部和前次级腭部表达。腭裂融合后，BMPR1AmRNA在浓缩的腭骨间充质祖细胞中表达上调。在小鼠发育中的腭间充质中，BMPR1A的组织特异性失活导致初级和前次级腭部细胞增殖减少，导致出生时前腭裂。在BMPR1A条件突变胚胎中，Msx1和Fgf10在前腭间充质中表达下调，Shh在前腭部上皮中表达下调，提示BMP信号调节腭部发育过程中间充质-上皮的相互作用。此外，上颌骨的腭突形成受阻，而腭突的形成明显延迟，导致突变小鼠的硬腭黏膜下裂开。我们的数据表明，BMP信号在腭骨形成过程中对腭间充质凝聚和成骨细胞分化的调节中起着关键作用。
Cleft palate, including submucous cleft palate, is among the most common birth defects in humans. While overt cleft palate results from defects in growth or fusion of the developing palatal shelves, submucous cleft palate is characterized by defects in palatal bones. In this report, we show that the Bmpr1a gene, encoding a type I receptor for bone morphogenetic proteins (Bmp), is preferentially expressed in the primary palate and anterior secondary palate during palatal outgrowth. Following palatal fusion, Bmpr1a mRNA expression was upregulated in the condensed mesenchyme progenitors of palatal bone. Tissue-specific inactivation of Bmpr1a in the developing palatal mesenchyme in mice caused reduced cell proliferation in the primary and anterior secondary palate, resulting in partial cleft of the anterior palate at birth. Expression of Msx1 and Fgf10 was downregulated in the anterior palate mesenchyme and expression of Shh was downregulated in the anterior palatal epithelium in the Bmpr1a conditional mutant embryos, indicating that Bmp signaling regulates mesenchymal-epithelial interactions during palatal outgrowth. In addition, formation of the palatal processes of the maxilla was blocked while formation of the palatal processes of the palatine was significantly delayed, resulting in submucous cleft of the hard palate in the mutant mice. Our data indicate that Bmp signaling plays critical roles in the regulation of palatal mesenchyme condensation and osteoblast differentiation during palatal bone formation.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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