A critical role for PDGFRα signaling in medial nasal process development.
A critical role for PDGFRα signaling in medial nasal process development.
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DOI：
10.1371/journal.pgen.1003851
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Soriano P
中科院分区：
文献类型：
--
作者：
He F;Soriano P
原始面部由神经嵴细胞（NCC）衍生的突起组成。内侧鼻突（MNP）产生上唇和犁鼻器，对于正常颅面发育至关重要，但 MNP 发育的机制仍然很大程度上未知。 PDGFRα 信号传导对于 NCC 的发展和颅面形态发生至关重要。在这项研究中，我们发现 PDGFRα 通过维持祖神经嵴细胞 (NCC) 的迁移和 MNP 细胞的增殖，是 MNP 发育所必需的。进一步研究表明，PI3K/Akt 和 Rac1 信号传导在 MNP 发育过程中介导 PDGFRα 功能。因此，我们将 PDGFRα 确立为 MNP 发育的新型调节因子，并阐明其下游信号通路在细胞和分子水平上的作用。颅面异常，包括唇裂和腭裂，是常见的出生缺陷。尽管这些通常与神经嵴发育缺陷相关，但中线缺陷更严重的表型表现是面部裂隙，但人们对此知之甚少。在这项工作中，我们表明PDGFRα突变体的面部裂表型与神经嵴细胞规范的缺陷无关，而是与内侧鼻突（MNP）（源自额鼻突出的面部原基）的后续缺陷相关。我们进一步表明，这种缺陷与细胞增殖和细胞迁移的改变有关，并且 PI3K 和 Rac1 信号传导对于维持正常的细胞增殖水平至关重要。最后，我们提供了Rac1在细胞运动水平以及PDGFRα调节下的趋化性水平上调节细胞迁移的证据。因此，我们将 PDGFRα 确立为 MNP 发育的新型调节因子，并阐明其下游信号通路在细胞和分子水平上的作用。
The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels. Craniofacial anomalies, including cleft lip and palate, are frequent birth defects. Although these are often associated with defects in neural crest development, the more severe phenotypic manifestations of midline defects is facial clefting, which is poorly understood. In this work, we show that the facial clefting phenotype of PDGFRα mutants is not associated with a defect in neural crest cell specification but rather a subsequent defect in the medial nasal process (MNP), a facial primordium derived from the frontonasal prominence. We further show that this defect is associated with alterations in both cell proliferation and cell migration, and that PI3K and Rac1 signaling are essential to maintain a normal level of cell proliferation. Last, we provide evidence that Rac1 regulates cell migration at the level of cell motility as well as chemotaxis under the regulation of PDGFRα. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.
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影响因子：
30.8
作者：
Ding, H;Wu, XL;Nagy, A
通讯作者：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Soriano, P
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