Morphogenesis and dysmorphogenesis of the appendicular skeleton.
Morphogenesis and dysmorphogenesis of the appendicular skeleton.
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DOI：
10.1002/bdrc.10012
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发表时间：
2003-05-01
影响因子：
2.1
通讯作者：
Tuan, Rocky S.
中科院分区：
文献类型：
--
作者：
Shum, Lillian;Coleman, Cynthia M.;Tuan, Rocky S.
软骨形态和分化是软骨内骨化(EO)骨骼发育的先决条件。多潜能间充质细胞经历了一个复杂的细胞命运决定过程，成为软骨前体细胞，并最终分化为软骨细胞。这些发育过程需要细胞-细胞和细胞-基质相互作用的协调。在这篇综述中，我们将肢芽发育作为软骨形成和分化的模型。我们总结了与轴构型、细胞凝聚、细胞命运决定、指骨形成、指间细胞凋亡、EO和关节形成有关的分子和细胞事件和信号通路。这些途径的相互联系的性质突出了遗传和致畸扰动的影响，这些扰动导致骨骼出生缺陷。综述的主题还包括遗传疾病和环境因素导致的肢体畸形，包括FGFR、GLI3、GDF5/CDMP1、Sox9和Cbfa1突变，以及沙利度胺和酒精诱导的畸形。了解软骨发育和EO的复杂相互作用有助于深入了解正常软骨、先天性疾病和病理性成人软骨的生物学机制。
Cartilage patterning and differentiation are prerequisites for skeletal development through endochondral ossification (EO). Multipotential mesenchymal cells undergo a complex process of cell fate determination to become chondroprogenitors and eventually differentiate into chondrocytes. These developmental processes require the orchestration of cell-cell and cell-matrix interactions. In this review, we present limb bud development as a model for cartilage patterning and differentiation. We summarize the molecular and cellular events and signaling pathways for axis patterning, cell condensation, cell fate determination, digit formation, interdigital apoptosis, EO, and joint formation. The interconnected nature of these pathways underscores the effects of genetic and teratogenic perturbations that result in skeletal birth defects. The topics reviewed also include limb dysmorphogenesis as a result of genetic disorders and environmental factors, including FGFR, GLI3, GDF5/CDMP1, Sox9, and Cbfa1 mutations, as well as thalidomide- and alcohol-induced malformations. Understanding the complex interactions involved in cartilage development and EO provides insight into mechanisms underlying the biology of normal cartilage, congenital disorders, and pathologic adult cartilage.