Neural crest cell-derived VEGF promotes embryonic jaw extension.
Neural crest cell-derived VEGF promotes embryonic jaw extension.
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DOI：
10.1073/pnas.1419368112
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发表时间：
2015-05-12
影响因子：
11.1
通讯作者：
Schwarz Q
中科院分区：
文献类型：
--
作者：
Wiszniak S;Mackenzie FE;Anderson P;Kabbara S;Ruhrberg C;Schwarz Q
颅面发育是一个复杂的形态发生事件，依赖于多种细胞类型之间的高度协调的相互作用。自从180多年前第一次描述下颌中的Meckel软骨以来，我们已经认识到这种特殊结构的扩张是正确的下颌骨发育的基础。在这里，我们证明了神经嵴细胞和血管之间的复杂关联在促进软骨细胞增殖和Meckel软骨的扩张中起着重要作用，这是正确的下颌骨形态发生的先决条件。这些发现提供了对影响下颌骨的高度流行的疾病的起源和潜在治疗的直接洞察。颌骨的形态发生依赖于胚胎发育过程中Meckel软骨的生长。然而，细胞类型和信号，促进软骨细胞增殖梅克尔软骨生长的定义很差。在这里，我们表明，神经嵴细胞（NCCs）及其衍生物提供了一个重要来源的血管内皮生长因子（VEGF），以提高颌骨血管化和稳定的主要下颌动脉。我们进一步在两个独立的小鼠模型中表明，血管促进Meckel软骨延伸。动脉组织与NCC或软骨细胞的共培养实验表明，NCC衍生的VEGF促进血管生长，并且血管分泌因子来指导软骨细胞增殖。计算机断层扫描和X线扫描的患者半侧颜面矮小也表明，颌骨发育不良与下颌动脉发育不全。我们的结论是，颅NCC及其衍生物提供了一个重要来源的VEGF，以支持血管生长在发展中的下巴，这反过来又是必不可少的正常软骨细胞增殖，因此下巴的延伸。
Craniofacial development is a complex morphogenic event that relies on highly orchestrated interactions between multiple cell types. Since the first description of Meckel’s cartilage in the lower jaw more than 180 years ago, we have come to realize that expansion of this specialized structure underpins correct mandible development. Here we demonstrate that an intricate association between neural crest cells and blood vessels plays an important role in promoting chondrocyte proliferation and expansion of Meckel’s cartilage as a prerequisite of correct mandibular morphogenesis. These findings provide direct insight into the origins and potential treatments of highly prevalent disorders affecting the mandible. Jaw morphogenesis depends on the growth of Meckel’s cartilage during embryogenesis. However, the cell types and signals that promote chondrocyte proliferation for Meckel’s cartilage growth are poorly defined. Here we show that neural crest cells (NCCs) and their derivatives provide an essential source of the vascular endothelial growth factor (VEGF) to enhance jaw vascularization and stabilize the major mandibular artery. We further show in two independent mouse models that blood vessels promote Meckel’s cartilage extension. Coculture experiments of arterial tissue with NCCs or chondrocytes demonstrated that NCC-derived VEGF promotes blood vessel growth and that blood vessels secrete factors to instruct chondrocyte proliferation. Computed tomography and X-ray scans of patients with hemifacial microsomia also showed that jaw hypoplasia correlates with mandibular artery dysgenesis. We conclude that cranial NCCs and their derivatives provide an essential source of VEGF to support blood vessel growth in the developing jaw, which in turn is essential for normal chondrocyte proliferation, and therefore jaw extension.
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影响因子：
56.9
作者：
Lammert, E;Cleaver, O;Melton, D
通讯作者：
Melton, D
影响因子：
56.9
作者：
Saito, Daisuke;Takase, Yuta;Takahashi, Yoshiko
通讯作者：
Takahashi, Yoshiko
影响因子：
56.9
作者：
Matsumoto, K;Yoshitomi, H;Zaret, KS
通讯作者：
Zaret, KS
DOI：
10.1016/0030-4220(73)90070-4
发表时间：
1973-01-01
期刊：
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY
影响因子：
--
作者：
POSWILLO, D
通讯作者：
POSWILLO, D
影响因子：
64.8
作者：
Kusumbe AP;Ramasamy SK;Adams RH
通讯作者：
Adams RH