Enteric nervous system development: migration, differentiation, and disease.
Enteric nervous system development: migration, differentiation, and disease.
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DOI：
10.1152/ajpgi.00452.2012
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发表时间：
2013-07-01
期刊：
影响因子：
--
通讯作者：
Heuckeroth RO
中科院分区：
文献类型：
--
作者：
Lake JI;Heuckeroth RO
肠神经系统（ENS）提供肠的内在神经支配，并且是周围神经系统的神经化学上最多样化的分支，由两层神经节和环绕胃肠道的纤维组成。ENS对生命至关重要，能够自主调节运动和分泌。模型生物的发育研究和ENS最常见的先天性疾病先天性巨结肠的遗传学研究，提供了ENS发育的详细了解。ENS起源于神经嵴，主要来自神经轴的迷走神经水平，其在肠壁内侵入、增殖和迁移，直到整个肠被肠神经嵴衍生细胞（ENCDC）定殖。在最初的迁移后，ENS通过响应引导因子和形态发生素进一步发育，这些引导因子和形态发生素同心地形成肠，分化成胶质细胞和神经元亚型，并连接在一起形成功能性神经系统。控制这一过程的分子，包括胶质细胞源性神经营养因子及其受体RET、内皮素（ET）-3及其受体内皮素受体B型以及转录因子如SOX 10和PHOX 2 B，是人类ENS发育所必需的。积极研究的重要领域包括引导ENCDC迁移的机制、内皮素受体B型的作用和下游信号、分化的控制、神经化学编码和轴突靶向。最近的工作也集中在疾病治疗，探索ENS干细胞的自然作用和调查潜在的治疗用途。通过改变胎儿的微环境来减少先天性巨结肠致病突变的发生率也是可能的。
The enteric nervous system (ENS) provides the intrinsic innervation of the bowel and is the most neurochemically diverse branch of the peripheral nervous system, consisting of two layers of ganglia and fibers encircling the gastrointestinal tract. The ENS is vital for life and is capable of autonomous regulation of motility and secretion. Developmental studies in model organisms and genetic studies of the most common congenital disease of the ENS, Hirschsprung disease, have provided a detailed understanding of ENS development. The ENS originates in the neural crest, mostly from the vagal levels of the neuraxis, which invades, proliferates, and migrates within the intestinal wall until the entire bowel is colonized with enteric neural crest-derived cells (ENCDCs). After initial migration, the ENS develops further by responding to guidance factors and morphogens that pattern the bowel concentrically, differentiating into glia and neuronal subtypes and wiring together to form a functional nervous system. Molecules controlling this process, including glial cell line-derived neurotrophic factor and its receptor RET, endothelin (ET)-3 and its receptor endothelin receptor type B, and transcription factors such as SOX10 and PHOX2B, are required for ENS development in humans. Important areas of active investigation include mechanisms that guide ENCDC migration, the role and signals downstream of endothelin receptor type B, and control of differentiation, neurochemical coding, and axonal targeting. Recent work also focuses on disease treatment by exploring the natural role of ENS stem cells and investigating potential therapeutic uses. Disease prevention may also be possible by modifying the fetal microenvironment to reduce the penetrance of Hirschsprung disease-causing mutations.
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