PDF(Pubmed)
Abstract：
The mandible is composed of several musculoskeletal tissues including bone, cartilage, and tendon that require precise patterning to ensure structural and functional integrity. Interestingly, most of these tissues are derived from one multipotent cell population called cranial neural crest cells (CNCCs). How CNCCs are properly instructed to differentiate into various tissue types remains nebulous. To better understand the mechanisms necessary for the patterning of mandibular musculoskeletal tissues we utilized the avian mutant talpid2 (ta2) which presents with several malformations of the facial skeleton including dysplastic tendons, mispatterned musculature, and bilateral ectopic cartilaginous processes extending off Meckel\'s cartilage. We found an ectopic epithelial BMP signaling domain in the ta2 mandibular prominence (MNP) that correlated with the subsequent expansion of SOX9+ cartilage precursors. These findings were validated with conditional murine models suggesting an evolutionarily conserved mechanism for CNCC-derived musculoskeletal patterning. Collectively, these data support a model in which cilia are required to define epithelial signal centers essential for proper musculoskeletal patterning of CNCC-derived mesenchyme.
摘要：
下颌骨由几种肌肉骨骼组织组成，包括骨骼，软骨，和肌腱，需要精确的图案，以确保结构和功能的完整性。有趣的是,这些组织中的大多数来自一种称为颅神经c细胞（CNCC）的多能细胞群。如何正确指示CNCC分化为各种组织类型仍然是模糊的。为了更好地了解下颌肌肉骨骼组织模式所必需的机制，我们利用了禽类突变体talpid2（ta2），它表现出面部骨骼的几种畸形，包括发育不良的肌腱，错误的肌肉组织，和双侧异位软骨突从Meckel软骨延伸。我们在ta2下颌突起（MNP）中发现了一个异位的上皮BMP信号结构域，该结构域与随后的SOX9软骨前体的扩增相关。这些发现已通过条件鼠模型得到验证，表明CNCC衍生的肌肉骨骼模式具有进化上保守的机制。总的来说，这些数据支持一个模型,在该模型中需要纤毛来定义上皮信号中心,这些信号中心对于CNCC来源的间充质的正确肌肉骨骼模式至关重要.
