Department of Pediatric Surgery, Massachusetts General Hospital, Massachusetts General Hospital for Children, Harvard Medical School, 55 Fruit St., WRN 1151, Boston, MA 02114, United States.
Department of Pediatric Surgery, Massachusetts General Hospital, Massachusetts General Hospital for Children, Harvard Medical School, 55 Fruit St., WRN 1151, Boston, MA 02114, United States.
Semin Pediatr Surg. 2022 Apr;31(2):151157. doi: 10.1016/j.sempedsurg.2022.151157. Epub 2022 Apr 18.
The enteric nervous system (ENS) is a rich network of neurons and glial cells that comprise the gastrointestinal tract's intrinsic nervous system and are responsible for controlling numerous complex functions, including digestion, transit, secretion, barrier function, and maintenance of a healthy microbiome. Development of a functional ENS relies on the coordinated interaction between enteric neural crest-derived cells and their environment as the neural crest-derived cells migrate rostrocaudally along the embryonic gut mesenchyme. Congenital or acquired disruption of ENS development leads to various neurointestinal diseases. Hirschsprung disease is a congenital neurocristopathy, a disease of the neural crest. It is characterized by a variable length of distal colonic aganglionosis due to a failure in enteric neural crest-derived cell proliferation, migration, differentiation, and/or survival. In this review, we will review the science of Hirschsprung disease, targeting an audience of pediatric surgeons. We will discuss the basic biology of normal ENS development, as well as what goes awry in ENS development in Hirschsprung disease. We will review animal models that have been integral to studying this disease, as well as current hot topics and future research, including genetic risk profiling, stem cell therapy, non-invasive diagnostic techniques, single-cell sequencing techniques, and genotype-phenotype correlation.
肠神经系统（ENS）是一个由神经元和神经胶质细胞组成的丰富网络，构成了胃肠道的内在神经系统，负责控制许多复杂的功能，包括消化、转运、分泌、屏障功能和维持健康的微生物组。功能性 ENS 的发育依赖于肠神经嵴衍生细胞与其环境之间的协调相互作用，因为神经嵴衍生细胞沿着胚胎肠道间质向头侧和尾侧迁移。ENS 发育的先天或后天破坏会导致各种神经肠道疾病。先天性巨结肠是一种先天性神经嵴病变，是一种神经嵴疾病。其特征是由于肠神经嵴衍生细胞的增殖、迁移、分化和/或存活失败，导致远端结肠无神经节细胞的长度可变。在这篇综述中，我们将以儿科外科医生为目标受众，回顾先天性巨结肠的科学。我们将讨论正常 ENS 发育的基础生物学，以及先天性巨结肠中 ENS 发育的异常情况。我们将回顾对研究这种疾病至关重要的动物模型，以及当前的热门话题和未来的研究，包括遗传风险分析、干细胞治疗、非侵入性诊断技术、单细胞测序技术和基因型-表型相关性。
